U.S. patent application number 16/480908 was filed with the patent office on 2020-02-06 for novel [1,2,4]triazolo[4,3-a]quinoxaline derivative, method for preparing same, and pharmaceutical composition for preventing or .
The applicant listed for this patent is Dong Wha Pharm. Co., Ltd., Korea Research Institute of Chemical Technology. Invention is credited to Imran Ali, Gildon Choi, Jung Hwan Kim, Seung Hwan Kim, Yong Tae Kim, Jin Soo Lee, Joo Yun Lee, Kwangho Lee, Jae-Kyung Lim, Whui Jung Park.
Application Number | 20200039984 16/480908 |
Document ID | / |
Family ID | 62979607 |
Filed Date | 2020-02-06 |
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United States Patent
Application |
20200039984 |
Kind Code |
A1 |
Lee; Kwangho ; et
al. |
February 6, 2020 |
Novel [1,2,4]Triazolo[4,3-a]Quinoxaline Derivative, Method For
Preparing Same, And Pharmaceutical Composition For Preventing Or
Treating BET Protein-Related Diseases, Containing Same As Active
Ingredient
Abstract
Provided are a novel [1,2,4]triazolo[4,3-a]quinoxaline
derivative, a method for preparing the same, and a pharmaceutical
composition for preventing or treating bromodomain extra-terminal
(BET) protein-related diseases including cancer and autoimmune
diseases, containing the same as an active ingredient.
Inventors: |
Lee; Kwangho; (Daejeon,
KR) ; Choi; Gildon; (Daejeon, KR) ; Ali;
Imran; (Daejeon, KR) ; Lee; Joo Yun; (Daejeon,
KR) ; Lee; Jin Soo; (Gyeonggi-do, KR) ; Park;
Whui Jung; (Gyeonggi-do, KR) ; Kim; Yong Tae;
(Gyeonggi-do, KR) ; Kim; Seung Hwan; (Gyeonggi-do,
KR) ; Kim; Jung Hwan; (Gyeonggi-do, KR) ; Lim;
Jae-Kyung; (Gyeonggi-do, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Dong Wha Pharm. Co., Ltd.
Korea Research Institute of Chemical Technology |
Seoul
Daejeon |
|
KR
KR |
|
|
Family ID: |
62979607 |
Appl. No.: |
16/480908 |
Filed: |
January 25, 2018 |
PCT Filed: |
January 25, 2018 |
PCT NO: |
PCT/KR2018/001128 |
371 Date: |
July 25, 2019 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 35/00 20180101;
C07D 487/04 20130101; A61K 31/4985 20130101; C07D 519/00 20130101;
A61K 31/4196 20130101 |
International
Class: |
C07D 487/04 20060101
C07D487/04; C07D 519/00 20060101 C07D519/00; A61P 35/00 20060101
A61P035/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 26, 2017 |
KR |
10-2017-0012823 |
Claims
1. A compound represented by formula 1, an optical isomer thereof
or a pharmaceutically acceptable salt thereof: ##STR00748## (In
formula 1, R.sup.1 is hydrogen, C.sub.1-20 straight or branched
alkyl nonsubstituted or substituted with one or more halogens, or
C.sub.6-20 aryl; R.sup.2 is hydrogen, C.sub.1-20 straight or
branched alkyl, or C.sub.1-20 straight or branched alkoxy; R.sup.3
is hydrogen, nitro, halogen, nonsubstituted or substituted
C.sub.1-20 straight or branched alkyl, nonsubstituted or
substituted C.sub.1-20 straight or branched alkoxy, 5-10 membered
heteroaryl nonsubstituted or substituted with one or more methyl
groups containing one or more heteroatoms selected from the group
consisting of N, O and S, ##STR00749## which forms 6 membered
cycloalkyl containing one or more heteroatoms selected from the
group consisting of S and O along with R.sup.4, wherein, the
substituted C.sub.1-20 straight or branched alkyl and the
substituted C.sub.1-20 straight or branched alkoxy can be
independently substituted with one or more substituents selected
from the group consisting of halogen, C.sub.1-3 straight or
branched alkoxy, 5-10 membered heterocycloalkyl containing one or
more heteroatoms selected from the group consisting of N, O and S,
and C.sub.6-10 aryl nonsubstituted or substituted with one or more
nitro groups, A.sup.1 is hydrogen, or C.sub.1-20 straight or
branched alkyl, B.sup.1 and B.sup.2 are independently hydrogen,
C.sub.1-20 straight or branched alkyl, diC.sub.1-3 straight or
branched alkylamino C.sub.1-3 straight or branched alkyl, or
C.sub.6-10 aryl, and B.sup.1 and B.sup.2 are linked to each other
to form 5-10 membered heterocycloalkyl nonsubstituted or
substituted with one or more benzyl groups containing one or more
heteroatoms selected from the group consisting of N, O and S,
C.sup.1 is hydrogen, C.sub.1-20 straight or branched alkyl, or
C.sub.1-20 straight or branched alkoxy, D.sup.1 and D.sup.2 are
independently hydrogen, hydroxy, C.sub.1-20 straight or branched
alkyl saturated or containing one or more carbon.ident.carbon
unsaturated bonds, C.sub.1-20 straight or branched alkyl
nonsubstituted or substituted with one or more cyano groups, or
C.sub.1-20 straight or branched alkylsulfonyl, E.sup.1 is
C.sub.1-20 straight or branched alkyl, or C.sub.6-10 aryl C.sub.1-5
straight or branched alkyl, F.sup.1 is C.sub.1-20 straight or
branched alkyl, or C.sub.6-10 aryl, G.sup.1 is C.sub.1-20 straight
or branched alkyl, or C.sub.6-10 aryl; R.sup.4 is hydrogen,
hydroxy, halogen, nitro, C.sub.1-20 straight or branched alkyl
nonsubstituted or substituted with one or more .dbd.S groups,
C.sub.1-20 straight or branched alkylsulfanyl nonsubstituted or
substituted with one or more oxo (.dbd.O) groups, C.sub.1-20
straight or branched alkylsulfonyl, 5-10 membered
heterocycloalkyloxy nonsubstituted or substituted with one or more
C.sub.1-5 straight or branched alkoxycarbonyl containing one or
more heteroatoms selected from the group consisting of N, O and S,
nonsubstituted or substituted 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, nonsubstituted or substituted C.sub.1-20 straight or
branched alkoxy, ##STR00750## wherein, the substituted 5-10
membered heteroaryl can be substituted with one or more
substituents selected from the group consisting of C.sub.1-3
straight or branched alkyl, C.sub.1-3 straight or branched alkoxy
and C.sub.1-3 straight or branched alkoxy C.sub.1-3 straight or
branched alkyl, wherein, the substituted C.sub.1-20 straight or
branched alkoxy can be substituted with one or more substituents
selected from the group consisting of halogen, cyano, C.sub.1-3
straight or branched alkoxy, nonsubstituted or substituted 5-10
membered heterocycloalkyl containing one or more heteroatoms
selected from the group consisting of N, O and S, and
nonsubstituted or substituted C.sub.6-10 aryl, wherein, the
substituted 5-10 membered heterocycloalkyl and the substituted
C.sub.6-10 aryl can be independently substituted with one or more
substituents selected from the group consisting of cyano,
##STR00751## C.sub.1-5 straight or branched alkoxycarbonyl, and 5-8
membered heteroaryl nonsubstituted or substituted with one or more
N groups, A.sup.3 is hydrogen, or C.sub.1-20 straight or branched
alkyl, B.sup.3 and B.sup.4 are independently hydrogen, C.sub.1-20
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, nonsubstituted or
substituted C.sub.6-10 aryl, nonsubstituted or substituted
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, and B.sup.3
and B.sup.4 are linked to each other to form 5-10 membered
heterocycloalkyl nonsubstituted or substituted with one or more
benzyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S, wherein, the substituted C.sub.6-10
aryl can be substituted with one or more substituents selected from
the group consisting of amine, halogen, C.sub.1-5 straight or
branched alkyl and C.sub.1-5 straight or branched alkoxy, C.sup.3,
C.sup.4 and C.sup.5 are independently hydrogen, amine, halogen,
C.sub.1-20 straight or branched alkyl, or C.sub.1-20 straight or
branched alkoxy, D.sup.3 and D.sup.4 are independently hydrogen,
hydroxy, C.sub.1-20 straight or branched alkyl saturated or
containing one or more carbon.ident.carbon unsaturated bonds,
C.sub.1-20 straight or branched alkyl nonsubstituted or substituted
with one or more cyano groups, or C.sub.1-20 straight or branched
alkylsulfonyl nonsubstituted or substituted with one or more
halogens, and D.sup.3 and D.sup.4 are linked to each other to form
5-10 membered heteroaryl containing one or more heteroatoms
selected from the group consisting of N, O and S, or 5-10 membered
heterocycloalkyl fused with 5 membered heteroaryl nonsubstituted or
substituted with one or more methyl groups or containing one S
group and one or more heteroatoms selected from the group
consisting of N, O and S, E.sup.3 is C.sub.1-20 straight or
branched alkyl, or C.sub.6-10 aryl C.sub.1-5 straight or branched
alkyl, F.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl, G.sup.3 is C.sub.1-20 straight or branched alkyl,
or C.sub.6-10 aryl, H.sup.3 is C.sub.6-10 aryl, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or 5-10 membered heteroaryl
nonsubstituted or substituted with one or more methyl groups
containing one or more heteroatoms selected from the group
consisting of N, O and S, I.sup.3 is diC.sub.1-3 straight or
branched alkylamino; R.sup.5 is hydrogen, halogen, C.sub.1-20
straight or branched alkyl nonsubstituted or substituted with one
or more halogens, or C.sub.1-20 straight or branched alkoxy;
R.sup.6 is hydroxy, ##STR00752## B.sup.5 and B.sup.6 are
independently hydrogen, C.sub.1-20 straight or branched alkyl,
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, or 5-10
membered heteroaryl C.sub.1-3 straight or branched alkyl containing
one or more heteroatoms selected from the group consisting of N, O
and S, D.sup.5 and D.sup.6 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens, E.sup.5 is
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkoxy saturated or containing one or more
carbon.ident.carbon unsaturated bonds, C.sub.3-10 cycloalkyloxy,
C.sub.3-10 cycloalkyl C.sub.1-3 straight or branched alkyl,
C.sub.3-10 cycloalkyl, C.sub.6-10 aryloxy, C.sub.6-10 aryl
C.sub.1-3 straight or branched alkoxy, C.sub.1-20 straight or
branched alkylsulfanyl, nonsubstituted or substituted C.sub.6-10
aryl, diC.sub.1-3 straight or branched alkylamino, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or nonsubstituted or
substituted 5-10 membered heteroaryl containing one or more N
groups, wherein, the substituted C.sub.1-20 straight or branched
alkyl can be substituted with one or more substituents selected
from the group consisting of hydroxy, halogen, C.sub.1-3 straight
or branched alkoxy, C.sub.1-3 straight or branched
alkylcarbonyloxy, C.sub.1-3 straight or branched alkoxycarbonyl,
hydroxycarbonyl, C.sub.6-10 aryl nonsubstituted or substituted with
one or more hydroxyl groups, 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, and ##STR00753## T.sup.1 and T.sup.2 are independently
hydrogen, C.sub.1-5 straight or branched alkyl, C.sub.1-5 straight
or branched alkoxycarbonyl, C.sub.1-5 straight or branched
alkylcarbonyl nonsubstituted or substituted with one or more
halogens or hydroxyl groups, and T.sup.1 and T.sup.2 are linked to
each other to form heterocycloalkyl nonsubstituted or substituted
with one or more hydroxyl groups or C.sub.1-3 straight or branched
alkyl groups containing one S group and one or more heteroatoms
selected from the group consisting of N, O and S, wherein, the
substituted C.sub.6-10 aryl and the substituted 5-10 membered
heteroaryl can be independently substituted with one or more
substituents selected from the group consisting of halogen, nitro,
C.sub.1-5 straight or branched alkyl and C.sub.1-5 straight or
branched alkoxy, F.sup.5 is C.sub.1-20 straight or branched alkyl,
C.sub.3-10 cycloalkyl, or C.sub.6-10 aryl nonsubstituted or
substituted with one or more halogens, G.sup.5 is C.sub.1-20
straight or branched alkyl, H.sup.5 is C.sub.1-20 straight or
branched alkyl, or C.sub.6-10 aryl nonsubstituted or substituted
with one or more halogens; M is C.sub.1-20 straight or branched
alkylene; and X is --NH--, or --O--).
2. The compound represented by formula 1, the optical isomer
thereof or the pharmaceutically acceptable salt thereof according
to claim 1, wherein: R.sup.1 is hydrogen, C.sub.1-10 straight or
branched alkyl nonsubstituted or substituted with one or more
halogens, or C.sub.6-10 aryl; R.sup.2 is hydrogen, C.sub.1-10
straight or branched alkyl, or C.sub.1-10 straight or branched
alkoxy; R.sup.3 is hydrogen, nitro, halogen, nonsubstituted or
substituted C.sub.1-10 straight or branched alkyl, nonsubstituted
or substituted C.sub.1-10 straight or branched alkoxy, 5-10
membered heteroaryl nonsubstituted or substituted with one or more
methyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S, ##STR00754## which forms 6 membered
cycloalkyl containing one or more heteroatoms selected from the
group consisting of S and O along with R.sup.4, wherein, the
substituted C.sub.1-10 straight or branched alkyl and the
substituted C.sub.1-10 straight or branched alkoxy can be
independently substituted with one or more substituents selected
from the group consisting of halogen, C.sub.1-3 straight or
branched alkoxy, 5-10 membered heterocycloalkyl containing one or
more heteroatoms selected from the group consisting of N, O and S,
and C.sub.6-10 aryl nonsubstituted or substituted with one or more
nitro groups, A.sup.1 is hydrogen, or C.sub.1-10 straight or
branched alkyl, B.sup.1 and B.sup.2 are independently hydrogen,
C.sub.1-10 straight or branched alkyl, diC.sub.1-3 straight or
branched alkylamino C.sub.1-3 straight or branched alkyl, or
C.sub.6-10 aryl, and B.sup.1 and B.sup.2 are linked to each other
to form 5-10 membered heterocycloalkyl nonsubstituted or
substituted with one or more benzyl groups containing one or more
heteroatoms selected from the group consisting of N, O and S,
C.sup.1 is hydrogen, C.sub.1-10 straight or branched alkyl, or
C.sub.1-10 straight or branched alkoxy, D.sup.1 and D.sup.2 are
independently hydrogen, hydroxy, C.sub.1-10 straight or branched
alkyl saturated or containing one or more carbon.ident.carbon
unsaturated bonds, C.sub.1-10 straight or branched alkyl
nonsubstituted or substituted with one or more cyano groups, or
C.sub.1-10 straight or branched alkylsulfonyl, E.sup.1 is
C.sub.1-10 straight or branched alkyl, or C.sub.6-10 aryl C.sub.1-5
straight or branched alkyl, F.sup.1 is C.sub.1-10 straight or
branched alkyl, or C.sub.6-10 aryl, G.sup.1 is C.sub.1-10 straight
or branched alkyl, or C.sub.6-10 aryl; R.sup.4 is hydrogen,
hydroxy, halogen, nitro, C.sub.1-10 straight or branched alkyl
nonsubstituted or substituted with one or more .dbd.S groups,
C.sub.1-10 straight or branched alkylsulfanyl nonsubstituted or
substituted with one or more oxo (.dbd.O) groups, C.sub.1-10
straight or branched alkylsulfonyl, 5-10 membered
heterocycloalkyloxy nonsubstituted or substituted with one or more
C.sub.1-5 straight or branched alkoxycarbonyl containing one or
more heteroatoms selected from the group consisting of N, O and S,
nonsubstituted or substituted 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, nonsubstituted or substituted C.sub.1-10 straight or
branched alkoxy, ##STR00755## wherein, the substituted 5-10
membered heteroaryl can be substituted with one or more
substituents selected from the group consisting of C.sub.1-3
straight or branched alkyl, C.sub.1-3 straight or branched alkoxy
and C.sub.1-3 straight or branched alkoxy C.sub.1-3 straight or
branched alkyl, wherein, the substituted C.sub.1-10 straight or
branched alkoxy can be substituted with one or more substituents
selected from the group consisting of halogen, cyano, C.sub.1-3
straight or branched alkoxy, nonsubstituted or substituted 5-10
membered heterocycloalkyl containing one or more heteroatoms
selected from the group consisting of N, O and S, and
nonsubstituted or substituted C.sub.6-10 aryl, wherein, the
substituted 5-10 membered heterocycloalkyl and the substituted
C.sub.6-10 aryl can be independently substituted with one or more
substituents selected from the group consisting of cyano,
##STR00756## C.sub.1-5 straight or branched alkoxycarbonyl, and 5-8
membered heteroaryl nonsubstituted or substituted with one or more
N groups, A.sup.3 is hydrogen, or C.sub.1-10 straight or branched
alkyl, B.sup.3 and B.sup.4 are independently hydrogen, C.sub.1-10
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, nonsubstituted or
substituted C.sub.6-10 aryl, nonsubstituted or substituted
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, and B.sup.3
and B.sup.4 are linked to each other to form 5-10 membered
heterocycloalkyl nonsubstituted or substituted with one or more
benzyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S, wherein, the substituted C.sub.6-10
aryl can be substituted with one or more substituents selected from
the group consisting of amine, halogen, C.sub.1-5 straight or
branched alkyl and C.sub.1-5 straight or branched alkoxy, C.sup.3,
C.sup.4 and C.sup.5 are independently hydrogen, amine, halogen,
C.sub.1-10 straight or branched alkyl, or C.sub.1-10 straight or
branched alkoxy, D.sup.3 and D.sup.4 are independently hydrogen,
hydroxy, C.sub.1-10 straight or branched alkyl saturated or
containing one or more carbon.ident.carbon unsaturated bonds,
C.sub.1-10 straight or branched alkyl nonsubstituted or substituted
with one or more cyano groups, or C.sub.1-10 straight or branched
alkylsulfonyl nonsubstituted or substituted with one or more
halogens, and D.sup.3 and D.sup.4 are linked to each other to form
5-10 membered heteroaryl containing one or more heteroatoms
selected from the group consisting of N, O and S, or 5-10 membered
heterocycloalkyl fused with 5 membered heteroaryl nonsubstituted or
substituted with one or more methyl groups or containing one S
group and one or more heteroatoms selected from the group
consisting of N, O and S, E.sup.3 is C.sub.1-10 straight or
branched alkyl, or C.sub.6-10 aryl C.sub.1-5 straight or branched
alkyl, F.sup.3 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl, G.sup.3 is C.sub.1-10 straight or branched alkyl,
or C.sub.6-10 aryl, H.sup.3 is C.sub.6-10 aryl, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or 5-10 membered heteroaryl
nonsubstituted or substituted with one or more methyl groups
containing one or more heteroatoms selected from the group
consisting of N, O and S, I.sup.3 is diC.sub.1-3 straight or
branched alkylamino; R.sup.5 is hydrogen, halogen, C.sub.1-10
straight or branched alkyl nonsubstituted or substituted with one
or more halogens, or C.sub.1-10 straight or branched alkoxy;
R.sup.6 is hydroxy, ##STR00757## B.sup.5 and B.sup.6 are
independently hydrogen, C.sub.1-10 straight or branched alkyl,
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, or 5-10
membered heteroaryl C.sub.1-3 straight or branched alkyl containing
one or more heteroatoms selected from the group consisting of N, O
and S, D.sup.5 and D.sup.6 are independently hydrogen, hydroxy,
C.sub.1-10 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-10 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-10 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens, E.sup.5 is
C.sub.1-10 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-10 straight
or branched alkoxy saturated or containing one or more
carbon.ident.carbon unsaturated bonds, C.sub.3-10 cycloalkyloxy,
C.sub.3-10 cycloalkyl C.sub.1-3 straight or branched alkyl,
C.sub.3-10 cycloalkyl, C.sub.6-10 aryloxy, C.sub.6-10 aryl
C.sub.1-3 straight or branched alkoxy, C.sub.1-10 straight or
branched alkylsulfanyl, nonsubstituted or substituted C.sub.6-10
aryl, diC.sub.1-3 straight or branched alkylamino, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or nonsubstituted or
substituted 5-10 membered heteroaryl containing one or more N
groups, wherein, the substituted C.sub.1-10 straight or branched
alkyl can be substituted with one or more substituents selected
from the group consisting of hydroxy, halogen, C.sub.1-3 straight
or branched alkoxy, C.sub.1-3 straight or branched
alkylcarbonyloxy, C.sub.1-3 straight or branched alkoxycarbonyl,
hydroxycarbonyl, C.sub.6-10 aryl nonsubstituted or substituted with
one or more hydroxyl groups, 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, and ##STR00758## T.sup.1 and T.sup.2 are independently
hydrogen, C.sub.1-5 straight or branched alkyl, C.sub.1-5 straight
or branched alkoxycarbonyl, C.sub.1-5 straight or branched
alkylcarbonyl nonsubstituted or substituted with one or more
halogens or hydroxyl groups, and T.sup.1 and T.sup.2 are linked to
each other to form heterocycloalkyl nonsubstituted or substituted
with one or more hydroxyl groups or C.sub.1-3 straight or branched
alkyl groups containing one S group and one or more heteroatoms
selected from the group consisting of N, O and S, wherein, the
substituted C.sub.6-10 aryl and the substituted 5-10 membered
heteroaryl can be independently substituted with one or more
substituents selected from the group consisting of halogen, nitro,
C.sub.1-5 straight or branched alkyl and C.sub.1-5 straight or
branched alkoxy, F.sup.5 is C.sub.1-10 straight or branched alkyl,
C.sub.3-10 cycloalkyl, or C.sub.6-10 aryl nonsubstituted or
substituted with one or more halogens, G.sup.5 is C.sub.1-10
straight or branched alkyl, H.sup.5 is C.sub.1-10 straight or
branched alkyl, or C.sub.6-10 aryl nonsubstituted or substituted
with one or more halogens; M is C.sub.1-10 straight or branched
alkylene; and X is --NH--, or --O--.
3. The compound represented by formula 1, the optical isomer
thereof or the pharmaceutically acceptable salt thereof according
to claim 1, wherein: R.sup.1 is --H, --CH.sub.3,
--CH.sub.2CH.sub.3, --CF.sub.3, ##STR00759## R.sup.2 is --H,
--CH.sub.3, or --OCH.sub.3; R.sup.3 is --H, --Cl, --F, --CH.sub.3,
--CF.sub.3, --OCH.sub.3, --OCF.sub.3, --NO.sub.2, --NH.sub.2,
##STR00760## which forms ##STR00761## along with R.sup.4; R.sup.4
is --H, --OH, --Cl, --F, --CH.sub.3, --OCH.sub.3, --SCH.sub.3,
--OCF.sub.3, --NO.sub.2, --NH.sub.2, ##STR00762## ##STR00763##
##STR00764## R.sup.5 is --H, --Cl, --CH.sub.3, --CF.sub.3, or
--OCH.sub.3; R.sup.6 is --NH.sub.2, hydroxy, ##STR00765##
##STR00766## ##STR00767## ##STR00768## ##STR00769## ##STR00770## M
is C.sub.3-4 straight or branched alkylene; and X is --NH--, or
--O--.
4. The compound represented by formula 1, the optical isomer
thereof or the pharmaceutically acceptable salt thereof according
to claim 1, wherein the compound represented by formula 1 is
selected from the group consisting of the following compounds: (1)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; (2)
N.sup.1-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diam-
ine dihydrochloride; (3)
2,2-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-propionamide; (4)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid isopropylester; (5)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-acetamid-
e; (6)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-is-
obutyramide; (7)
3-methyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-butyramide; (8)
3,3-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-butyramide; (9)
2-(R)-hydroxy-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (10)
2-(S)-hydroxy-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (11)
N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-benzam-
ide; (12)
2-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-benzamide; (13)
2,6-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; (14)
4-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; (15)
3-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; (16)
3,4-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; (17)
2,3-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; (18)
3,5-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; (19)
2,6-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-nicotinamide; (20)
6-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-nicotinamide; (21)
2-chloro-6-methyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-nicotinamide; (22)
1-tert-butyl-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-urea; (23)
1-(4-fluoro-phenyl)-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-urea; (24)
1-(3-fluoro-phenyl)-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-urea; (25)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid benzylester; (26)
[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; (27)
N.sup.1-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)but-
ane-1,4-diamine ditrifluoroacetic acid; (28)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2,2-dimethyl-propionamide; (29)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-isobutyramide; (30)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; (31)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; (32)
2-chloro-N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-benzamide; (33)
6-chloro-N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-nicotinamide; (34)
[4-(1,7,8-trimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-c-
arbamic acid-tert-butylester; (35)
[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; (36)
N.sup.1-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; (37)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; (38)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(R)-hydroxy-3-methyl-butyramide; (39)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(S)-hydroxy-3-methyl-butyramide; (40)
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carb-
amic acid-tert-butylester; (41)
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butane]-1,4-
-diamine dihydrochloride; (42)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-2,-
2-dimethyl-propionamide; (43)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-is-
obutyramide; (44)
1-tert-butyl-3-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-urea; (45)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-be-
nzamide; (46)
1-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-3--
phenyl-urea; (47)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (48)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-1,4-diamine dihydrochloride; (49)
N-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-2,2-dimethyl-propionamide; (50)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-isobutyramide; (51)
N-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; (52)
1-tert-butyl-3-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-urea; (53)
1-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-3-phenyl-urea; (54)
[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (55)
N.sup.1-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)butane--
1,4-diamine hydrochloride; (56)
N-[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; (57)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (58)
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (59)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; (60)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (61)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid ethylester; (62)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; (63)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-sec-butylester; (64)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid propylester; (65)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid allylester; (66)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid cyclopentylester; (67)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid phenylester; (68)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid benzylester; (69)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-acetamide; (70)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-isobutyramide; (71) 3-methyl-buten-2-oic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (72) butene-2-oic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (73) 3-methyl-pentanoic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (74)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (75)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3,3-dimethyl-butyramide; (76) cyclopropanecarboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (77)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methyl-butyramide; (78)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-ethyl-butyramide; (79) 4-methyl-pentanoic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (80)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methoxy-acetamide; (81)
3-cyclopentyl-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-propionamide; (82)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-(R)-hydroxy-3-methyl-butyramide; (83)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-(S)-hydroxy-3-methyl-butyramide; (84)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-thiophene-2-yl-acetamide; (85)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-furan-2-yl-acetamide; (86)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-phenyl-acetamide; (87) acetic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamoyl]-methylester; (88)
1-tert-butyl-3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-urea; (89)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-ethyl-urea; (90)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-3-isopropyl-urea; (91)
3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-1,1-dimethyl-urea; (92) morpholine-4-carboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (93)
1-cyclohexyl-3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-urea; (94)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-phenyl-urea; (95)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide; (96)
4-tert-butyl-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-benzamide; (97)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methoxy-benzamide; (98)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-4-fluoro-benzamide; (99)
2-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; (100)
4-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; (101)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-4-nitro-benzamide; (102)
2,3-dichloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-benzamide; (103)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-isonicotinamide; (104)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-nicotinamide; (105) pyridine-2-carboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; (106)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-fluoro-benzamide; (107)
6-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-nicotinamide; (108)
2-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; (109)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-methanesulfonamide; (110)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-thiocarbamic acid-S-isopropylester; (111)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid-tert-butylester; (112)
N.sup.1-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl)-butane-1,4-diamine dihydrochloride; (113)
N-[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-2,2-dimethyl-propionamide; (114)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid isopropylester; (115)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid isobutylester; (116)
N-[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-3,3-dimethyl-butyramide; (117)
[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; (118)
N.sup.1-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine dihydrochloride; (119)
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; (120)
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid isobutylester; (121)
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; (122)
N.sup.1-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid; (123)
N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; (124)
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3,3-dimethyl-butyramide; (125)
2-(R)-hydroxy-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (126)
2-(S)-hydroxy-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (127)
N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-benzamide; (128)
2-chloro-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; (129)
2-chloro-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-6-methyl-nicotinamide; (130)
{4-[6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-b-
utyl}-carbamic acid-tert-butylester; (131)
N.sup.1-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (132)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; (133)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (134)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; (135)
N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (136)
2-(R)-hydroxy-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (137)
2-(S)-hydroxy-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (138)
N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide;
(139)
2-fluoro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino)-butyl]-benzamide; (140)
2-chloro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; (141)
2-chloro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; (142)
[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid-tert-butylester; (143)
N.sup.1-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; (144)
[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isopropylester; (145)
N-[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (146)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (147)
N.sup.1-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (148)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; (149)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (150)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; (151)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (152)
2-(R)-hydroxy-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (153)
2-(S)-hydroxy-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (154)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide; (155)
2-fluoro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; (156)
2-chloro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; (157)
2-chloro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; (158)
[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (159)
N.sup.1-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine difluoroacetic acid; (160)
N-[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (161)
[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (162)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester; (163)
N.sup.1-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; (164)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2,2-dimethyl-propionamide; (165)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid isopropylester; (166)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; (167)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3,3-dimethyl-butyramide; (168)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid isobutylester; (169)
1-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-tert-butyl-urea; (170)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-benzamide; (171)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-chloro-benzamide; (172)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-chloro-6-methyl-nicotinamide; (173)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl-carbamic acid-tert-butylester; (174)
N.sup.1-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; (175)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; (176)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; (177)
N-[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl-3-methyl-butyramide; (178)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid-tert-butylester; (179)
N.sup.1-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; (180)
2,2-dimethyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyc-
lopenta[a]anthracene-4-ylamino)-butyl]-propionamide; (181)
3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclope-
nta[a]anthracene-4-ylamino)-butyl]-butyramide; (182)
2-(R)-hydroxy-3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-te-
traaza-cyclopenta[a]anthracene-4-ylamino)-butyl]-butyramide; (183)
2-(S)-hydroxy-3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-te-
traaza-cyclopenta[a]anthracene-4-ylamino)-butyl]-butyramide; (184)
acetic
acid-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene-4-ylamino)-butyl]-carbamoyl]-methylester; (185)
N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]ant-
hracene-4-ylamino)-butyl]-2-thiophene-2-yl-acetamide; (186)
N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]ant-
hracene-4-ylamino)-butyl]-benzamide; (187)
2-chloro-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclope-
nta[a]anthracene-4-ylamino)-butyl]-benzamide; (188)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid isopropylester; (189)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid isobutylester; (190)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid cyclopentylester; (191)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid phenylester; (192)
1-isopropyl-3-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cycl-
openta[a]anthracene-4-ylamino)-butyl]-urea; (193)
[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; (194)
N.sup.1-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; (195)
3-methyl-N-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; (196) 3-methyl-pentanoic
acid-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; (197)
4-(4-tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-7-carboxylic acid methylester; (198)
4-(4-amino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carbo-
xylic acid methylester ditrifluoroacetic acid; (199)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid methylester; (200)
4-[(4-tert-butoxycarbamoylamino)-butylamino]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-7-carboxylic acid; (201)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid; (202)
[4-(7-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester; (203)
[4-(7-tert-butylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-carbamic acid-tert-butylester; (204)
4-(4-isobutyramido-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-7-carboxylic acid isopropylamide; (205)
4-(4-benzoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
7-carboxylic acid isopropylamide; (206)
{4-[7-(2-dimethylamino-ethylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (207)
4-(4-benzoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
7-carboxylic acid-(2-dimethylamino-ethyl)-amide; (208)
N-{4-[7-(4-benzyl-piperazine-1-carbonyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-benzamide; (209)
N-{4-[1-methyl-7-(piperazine-1-carbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-benzamide; (210)
[4-(7-benzylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; (211)
{4-[7-(4-chloro-benzylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid-tert-butylester; (212)
[4-(1-methyl-7-phenylcarbamoyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; (213)
{4-[7-(2-amino-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-carbamic acid-tert-butylester; (214)
{4-[7-(2-amino-4-methyl-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (215)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-phenyl)-amide; (216)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-4-methyl-phenyl)-amide; (217)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-4,5-dimethoxy-phenyl)-amide;
(218)
{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester; (219)
{4-[1-methyl-7-(5-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (220)
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (221)
N.sup.1-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid;
(222)
3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (223)
3-methyl-N-{4-[1-methyl-7-(5-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (224)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; (225)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; (226)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; (227)
N-{4-[7-(5,6-dimethoxy-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (228)
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid propylester; (229)
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid cyclopentylester; (230)
2,2-dimethyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-propionamide; (231)
acetic
acid-1-{4-[7-(1-methyl-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-1-methyl-ethylester;
(232)
2-hydroxy-N-{4-(7-(1-methyl-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino)-butyl}-2-methyl-propionamide;
(233)
2,2-difluoro-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (234)
2-(S)-hydroxy-3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-
-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide;
(235)
2-(R)-hydroxy-3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzimidazole-2-yl)--
[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide;
(236) 4-methyl-pentanoic
acid-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-amide; (237)
2-methoxy-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-benzamide; (238)
1-isopropyl-3-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tri-
azolo[4,3-a]quinoxaline-4-ylamino]-butyl}-urea; (239)
1-cyclohexyl-3-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-urea; (240)
3-methyl-N-{4-[1-methyl-7-(1-propyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (241)
N-(4-{7-[1-(2-methoxy-ethyl)-1H-benzoimidazole-2-yl]-1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino}-butyl)-3-methyl-butyramide; (242)
[4-(1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; (243)
[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; (244)
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide; (245)
N-[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide; (246)
[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester; (247)
N-[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide; (248)
N-[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-benzamide; (249)
[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; (250)
N-[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; (251)
N-[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-benzamide; (252)
3-methyl-N-[4-(1-methyl-7-methylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; (253)
3-methyl-N-[4-(1-methyl-7-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; (254)
N-{4-[7-(3-cyano-propylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-3-methyl-butyramide; (255)
N-{4-[7-(3-isopropyl-ureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino]-butyl}-3-methyl-butyramide; (256)
N-{4-[7-(3-isopropyl-thioureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; (257)
N-[4-(7-methanesulfonylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; (258)
3-methyl-N-{4-[1-methyl-7-(2,2,2-trifluoro-ethanesulfonylamino)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (259)
3-methyl-N-{4-[1-methyl-7-(propane-2-sulfonylamino)-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-butyramide; (260)
[4-(7-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester;
(261)
{4-[7-(4-chloro-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester; (262)
{4-[7-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester; (263)
[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; (264)
N.sup.1-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid; (265)
2,2-dimethyl-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide; (266)
3,3-dimethyl-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide; (267)
N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; (268)
2-chloro-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-benzamide; (269)
[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; (270)
N.sup.1-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid; (271)
2,2-dimethyl-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide; (272)
3,3-dimethyl-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide; (273)
N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; (274)
2-chloro-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-benzamide; (275)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; (276)
N.sup.1-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid; (277)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; (278)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid isopropylester; (279)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid isobutylester; (280)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-sec-butylester; (281)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-isobutyramide; (282) cyclopropanecarboxylic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; (283) butene-2-oic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; (284) 3-methyl-butene-2-oic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; (285)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-butyramide; (286)
2-(S)-fluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; (287)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3,3-dimethyl-butyramide; (288) 4-methyl-pentanoic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; (289) 3-methyl-pentanoic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; (290)
2-ethyl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-butyramide; (291)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-methyl-butyramide; (292)
2,2,3,3,4,4,4-heptafluoro-N-[4-(7-methoxy-1l-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino)-butyl]-butyramide; (293)
3,3,3-trifluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-2,2-dimethyl-propaneamide; (294)
2,2-difluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; (295)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-propaneamide; (296) acetic
acid-1l-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butylcarbamoyl]-1-methyl-ethylester; (297)
2-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-2-methyl-propionamide; (298)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (299)
2-(S)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (300)
2-(R)-methoxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (301)
2-(S)-methoxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (302)
2-(S)-bromo-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-3-methyl-butyramide; (303) acetic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butylcarbamoyl]-methylester; (304)
2-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-acetamide; (305)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-malonamic acid ethylester; (306)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-malonamic acid; (307)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-thiophene-2-yl-acetamide; (308)
2-furan-2-yl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-acetamide; (309)
3-cyclopentyl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-propionamide; (310)
{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tylcarbamoyl]-2-methyl-propyl}-carbamic acid-tert-butylester; (311)
2-amino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; (312)
2-(R)-dimethylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl]-3-methyl-butyramide; (313)
2-(S)-dimethylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl]-3-methyl-butyramide; (314)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-2-(S)-morpholine-4-yl-butyramide; (315)
2-(S)-(3-hydroxy-pyrrolidine-1-yl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (316)
2-(S)-(4-hydroxy-piperidine-1-yl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (317)
2-(S)-[4-(2-hydroxy-ethyl)-piperidine-1-yl]-N-[4-(7-methoxy-1-methyl-[1,2-
,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide;
(318)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid isobutylester;
(319)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid propylester; (320)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid isopropylester;
(321)
(S)-2-(S)-fluoro-N-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl
carbamoyl]-2-methyl-propyl}-3-methyl-butyramide; (322)
(S)--N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-3-methyl-2-(3-methyl-butyrylamino)-butyramide; (323)
(S)-2-(2,2-dimethyl-propionylamino)-N-[4-(7-methoxy-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (324)
2-(S)-(2(S)-hydroxy-propionylamino)-N-[4-(7-methoxy-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (325)
{2-(S)-(4-hydroxy-phenyl)-1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-4-ylamino)-butylcarbamoyl]-ethyl}-carbamic
acid-tert-butylester; (326)
2-(S)-amino-3-(4-hydroxy-phenyl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino)-butyl]-propionamide; (327)
2-(S)-methanesulfonylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (328)
2-fluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; (329)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-phenyl-acetamide; (330)
1-isopropyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-urea; (331)
1-tert-butyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-urea; (332)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid cyclopentylester; (333)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid phenylester; (334)
3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-1,1-dimethyl-urea; (335)
1-cyclohexyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-urea; (336)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-thiocarbamic acid-S-isopropylester; (337)
1-isopropyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-thiourea; (338)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-methanesulfonamide; (339)
N-{4-[7-methoxy-1-methyl-8-(4-nitro-benzyl)-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-3-methyl-butyramide; (340)
N-[4-(7-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-butyramide; (341)
N-{4-[7-(4-cyano-benzyloxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-3-methyl-butyramide; (342)
N-{4-[7-(3-cyano-propoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-3-methyl-butyramide; (343)
3-methyl-N-{4-[1-methyl-7-(tetrahydro-pyran-2-ylmethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; (344)
3-methyl-N-{4-[1-methyl-7-(tetrahydro-pyran-4-yloxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-butyramide; (345)
4-{1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3-a]-
quinoxaline-7-yloxy}-piperidine-1-carboxylic acid-tert-butylester;
(346)
N-[4-(7-benzyloxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide; (347)
N-(4-{7-[4-(N-hydroxycarbaimidolyl)-benzoyl]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino}-butyl)-3-methyl-butyramide; (348)
3-methyl-N-(4-{1-methyl-7-[4-(2H-tetrazol-5-yl)-benzyloxy]-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino}-butyl)-butyramide; (349)
3-methyl-N-(4-{1-methyl-7-[4-(2-methyl-2H-tetrazolo-5-yl)-benzyloxy]-[1,2-
,4]triazolo[4,3-a]quinoxaline-4-ylamino}-butyl)-butyramide; (350)
benzoic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3--
a]quinoxaline-7-yl-ester; (351) morpholine-4-carboxylic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3--
a]quinoxaline-7-yl-ester; (352) 3-methyl-thiophene-2-carboxylic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3--
a]quinoxaline-7-yl-ester; (353) dimethyl-thiocarbamic
acid-O-{1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4-
,3-a]quinoxaline-7-yl}-ester; (354)
[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; (355)
N.sup.1-(1-methyl-(7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
l)-butane-1,4-diamine ditrifluoroacetic acid; (356)
3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; (357)
2-(S)-fluoro-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino)-butyl]-butyramide; (358)
2-(S)-hydroxy-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino)-butyl]-butyramide; (359)
N-[4-(7-methanesulfinyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; (360)
N-[4-(7-methanesulfonyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; (361)
[4-(7-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (362)
4-(7-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-carbami-
c acid-tert-butylester; (363)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-tert-butylester; (364)
N-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl]--
butane-1,4-diamine ditrifluoroacetic acid; (365)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-3-methyl-butyramide; (366)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid isopropylester; (367)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid propylester; (368)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-sec-butylester; (369)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid isobutylester; (370)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid allylester; (371)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid cyclopentylester; (372)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid phenylester; (373)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid benzylester; (374)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-acetamide; (375)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-2,2-dimethyl-propionamide; (376)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-isobutyramide; (377) cyclopropanecarboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (378) 3-methyl-butene-2-oic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (379) butene-2-oic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (380)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-methyl-butyramide; (381)
2-ethyl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-butyramide; (382)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-3,3-dimethyl-butyramide; (383) 4-methyl-pentanoic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (384) acetic
acid-1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-1-methyl-ethylester; (385)
2-hydroxy-N-{4-(7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino)-butyl}-2-methyl-propionamide; (386) acetic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butylcarbamoyl}-methylester; (387)
2-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-acetamide;
(388)
2-(R)-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (389)
2-(S)-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (390)
2-(R)-methoxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (391)
2,2-difluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-butyramide; (392)
3,3,3-trifluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-2,2-dimethyl-propionamide; (393)
3-cyclopentyl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-propionamide; (394)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-malonamic acid ethylester; (395)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-malonamic acid; (396)
(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid-tert-butylester; (397)
2-amino-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (398)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
isobutylester; (399)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
propylester; (400)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
isopropylester; (401)
(S)--N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-3-methyl-2-(3-methyl-butyrylamino)-butyramide;
(402)
(S)-2-(2,2-dimethyl-propionylamino)-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[-
1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide;
(403)
2-(S,R)-hydroxy-N-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-3-methyl-
-butyramide; (404)
2-(S,S)-hydroxy-N-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-3-methyl-butyr-
amide; (405)
2-(S)-methanesulfonylamino-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (406)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-thiophene-2-yl-acetamide; (407)
2-furan-2-yl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-acetamide; (408)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-benzamide; (409)
2-fluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; (410)
3-fluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; (411)
2-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; (412)
2-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; (413)
2,3-dichloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-benzamide; (414)
2-methoxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-benzamide; (415)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-4-nitro-butyramide; (416) pyridine-2-carboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (417)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-nicotinamide; (418)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-isonicotinamide; (419)
6-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-nicotinamide; (420)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-phenyl-acetamide; (421)
3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-1,1-dimethyl-urea; (422)
1-isopropyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-urea; (423)
1-ethyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-urea; (424)
1-tert-butyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-urea; (425) morpholine-4-carboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; (426)
1-cyclohexyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-urea; (427)
3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-1-phenyl-urea; (428)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-thiocarbamic acid-S-isopropylester; (429)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-methanesulfonamide; (430)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid-tert-butylester; (431)
N.sup.1-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-yl]-butane-1,4-diamine trifluoroacetic acid; (432)
3-methyl-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-butyramide; (433)
2,2-dimethyl-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino]-butyl}-propionamide; (434)
2-(R)-hydroxy-N-{4-[7-(2-morpholine-4-yl-ethoxy)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (435)
2-(S)-hydroxy-N-{4-[7-(2-morpholine-4-yl-ethoxy)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (436)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid isopropylester; (437)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid cyclopentylester; (438)
N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-2-thiophene-2-yl-acetamide; (439)
2-chloro-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-benzamide; (440)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (441)
N.sup.1-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine dihydrochloride; (442)
N-[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-3-methyl-butyramide; (443)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isopropylester; (444)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isobutylester; (445)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid cyclopentylester; (446)
N-[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-2-thiophene-2-yl-acetamide; (447)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; (448)
N.sup.1-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; (449)
N-[-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide; (450)
N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-methyl-butyramide; (451)
N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-thiophene-2-yl-acetamide; (452)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; (453)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid cyclopentylester; (454)
2-chloro-N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-benzamide; (455)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (456)
N.sup.1-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (457)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (458)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide; (459)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; (460)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine dihydrochloride; (461)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; (462)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid isobutylester; (463)
N-[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-2-thiophene-2-yl-acetamide; (464)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (465)
N.sup.1-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (466)
N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; (467)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (468)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; (469)
N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (470)
2-chloro-N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-yl)-butyl]-benzamide; (471)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid-tert-butylester; (472)
N.sup.1-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; (473)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isopropylester; (474)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isobutylester; (475)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid cyclopentylester; (476)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; (477)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-2,2-dimethyl-propionamide; (478)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (479)
2-(S)-hydroxy-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (480)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-2-thiophene-2-yl-acetamide; (481)
2-chloro-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino)-butyl]-benzamide; (482)
1-cyclohexyl-3-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino)-butyl]-urea; (483)
{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester; (484)
N.sup.1-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; (485)
N-{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; (486)
[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; (487)
N.sup.1-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; (488)
3-methyl-N-[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; (489) 3-methyl-pentanoic
acid-[4-(6,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; (490)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; (491)
N.sup.1-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine dihydrochloride; (492)
N-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; (493)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isobutylester; (494)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isopropylester; (495) 3-methyl-pentanoic
acid-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; (496)
N-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-2-thiophene-2-yl-acetamide; (497)
[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; (498)
N.sup.1-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
l)-butane-1,4-diamine dihydrochloride; (499)
3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-butyramide; (500)
2-(S)-fluoro-3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino)-butyl]-butyramide; (501)
3-methyl-pentanoic
acid-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-amide; (502)
(S)-{2-methyl-1-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butylcarbamoyl]-propyl}-carbamic
acid-tert-butylester; (503)
2-(S)-amino-3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino)-butyl]-butyramide hydrochloride;
(504)
(S)-2-(2-(S)-hydroxy-propionylamino)-3-methyl-N-[4-(1-methyl-7-morpholine-
-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-butyramide
hydrochloride; (505)
2-(S)-methanesulfonylamino-3-methyl-N-[4-(1-methyl-7-morphonyl-4-yl-[1,2,-
4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-butyramide; (506)
[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid isopropylester; (507)
N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-2-thiophene-2-yl-acetamide; (508)
{4-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (509)
N.sup.1-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; (510)
N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-3-methyl-butyramide;
(511)
N-{4-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-2-(S)-fluoro-3-methyl-butyramide;
(512)
N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; (513)
(S)-(2-methyl-1-{4-[1-methyl-7-(2,6-dimethyl-morpholine-4-yl)-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-propyl)-carbamic
acid-tert-butylester; (514)
2-(S)-amino-N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide
hydrochloride; (515)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid isobutylester; (516)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid propylester; (517)
(S)--N-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-2-(S)-fluoro--
3-methyl-butyramide; (518)
(S)--N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-3-methyl-2-(3-methyl-butyrylamino)-butyram-
ide; (519)
(S)--N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]tri-
azolo[4,3-a]quinoxaline-4-ylamino]-butyl}-2-(2,2-dimethyl-propionylamino)--
3-methyl-butyramide; (520)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid isopropylester; (521)
{[4-(1-methyl-7-thiomorpholine-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-carbamic acid-tert-butylester; (522)
N.sup.1-(1-methyl-7-thiomorphonyl-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl)-butane-1,4-diamine ditrifluoroacetic acid; (523)
3-methyl-N-[4-(1-methyl-7-thiomorpholine-4-yl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino)-butyl]-butyramide; (524)
N-[4-(7-thiomorphonyl-4-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-2-(R)-hydroxy-3-methyl-butyramide; (525)
N-[4-(7-thiomorphonyl-4-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-2-(S)-hydroxy-3-methyl-butyramide; (526)
{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino]-butyl}-carbamic
acid-tert-butylester; (527)
N.sup.1-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic
acid; (528)
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4-
]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide;
(529)
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-2-(S)-fluoro-3-methyl-butyramide;
(530)
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-8-carboxylic acid methylester; (531)
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-carboxylic acid; (532)
[4-(8-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester; (533)
[4-(8-carbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; (534)
4-(4-isobutyramido-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-8-carboxylic acid isopropylamide; (535)
4-(4-benzylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-
-carboxylic acid isopropylamide; (536)
{4-[8-(2-dimethylamino-ethylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; (537)
4-(4-benzoylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-carboxyli-
c acid-(2-dimethylamino-ethyl)-amide; (538)
[4-(1-methyl-8-phenylcarbamoyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; (539)
N-{4-[8-(4-benzyl-piperazine-1-carbonyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-benzamide; (540)
N-{4-[1-methyl-8-(piperazine-1-carbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-benzamide; (541)
[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; (542)
[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; (543)
[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester; (544)
N-[4-(4-aminobutylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-yl]-
-isobutyramide ditrifluoroacetic acid; (545)
N-[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide; (546)
[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; (547)
N-[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; (548)
N-[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-benzamide; (549)
N-[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-benzamide; (550)
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide; (551)
N-[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide; (552)
3-methyl-N-[4-(1-methyl-8-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; (553)
N-{4-[8-(3-cyano-propylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-3-methyl-butyramide; (554)
N-{4-[8-(3-ethyl-thioureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino]-butyl}-3-methyl-butyramide; (555)
N-[4-(7-methoxy-1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; (556)
N-[4-(8-amino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; (557)
N-[4-(7-methoxy-1-methyl-8-methylamino-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (558)
N-[4-(8-hydroxyamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-3-methyl-butyramide; (559)
N-[4-(7-methoxy-1-methyl-8-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; (560)
N-[4-(7-methoxy-1-methyl-8-prop-2-ylamino-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-3-methyl-butyramide; (561)
N-{4-[8-(3-isopropyl-ureido)-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-3-methyl-butyramide; (562)
N-{4-[7-methoxy-1-methyl-8-(3-methyl-butyrylamino)-[1,2,4]triazolo[4,3-a]-
quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (563)
N-{7-methoxy-1-methyl-4-[4-(3-methyl-butyrylamino)-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-ylamino]-butyl}-3,3-dimethyl-butyramide; (564)
N-{4-[7-methoxy-1-methyl-8-(3-phenyl-ureido)-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-3-methyl-butyramide; (565)
N-[4-(8-methanesulfonylamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino)-butyl]-3-methyl-butyramide; (566)
N-[4-(8-dimethanesulfonylamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; (567)
N-{4-[7-methoxy-1-methyl-8-(2-methyl-propane-1-sulfonylamino)-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (568)
N-{4-[7-methoxy-1-methyl-8-(3-phenyl-ureido)-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-3-methyl-butyramide; (569)
N-{4-[8-(3-isopropyl-thioureido)-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (570)
{4-[8-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester; (571)
[4-(8-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; (572)
[4-(8-fluoro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; (573)
[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; (574)
N-[4-(8-fluoro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; (575)
N-[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; (576)
N-{4-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (577)
N-{4-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; (578)
{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester; (579)
N.sup.1-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; (580)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; (581)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; (582)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; (583)
{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester; (584)
N.sup.1-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; (585)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; (586)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; (587)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; (588)
N.sup.1-[7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl]-butane-1,4-diamine ditrifluoroacetic acid; (589)
[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid isopropylester; (590)
N-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; (591) 3-methyl-pentanoic
acid-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-amide; (592)
N.sup.1-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; (593)
N-[4-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; (594)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; (595)
N.sup.1-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; (596)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; (597)
N-[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; (598)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; (599)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; (600)
N.sup.1-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; (601)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isopropylester; (602)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isobutylester; (603)
N-[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; (604)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; (605)
N.sup.1-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; (606)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; (607)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; (608)
N-[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; (609)
[4-([1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; (610)
[4-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (611)
N.sup.1-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine; (612)
N-[4-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-acetamide; (613)
[4-(1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; (614)
N.sup.1-(1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diami-
ne; (615)
[4-(1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; (616)
N.sup.1-(1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-d-
iamine; (617)
[4-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; (618)
N.sup.1-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diam-
ine; (619)
N-[4-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-acetamide; (620)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; (621)
N.sup.1-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine ditrifluoroacetic acid; (622)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-3-methyl-butyramide; (623)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isopropylester; (624)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isobutylester; (625)
[4-(7-methoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; (626)
N.sup.1-(7-methoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; (627)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-3-methyl-butyramide; (628)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; (629)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; (630)
4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butan-1-ol;
(631) 2,2-dimethyl-propionic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
(632) isobutyric
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-este-
r; (633) 3,3-dimethyl-butyric
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-este-
r; (634) benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
(635) 4-chloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
(636) 2,3-dichloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
(637) 2-chloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
(638)
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-bu-
tyl-carbamic acid-tert-butylester; (639)
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butylami-
ne ditrifluoroacetic acid; (640)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-
]-3-methyl-butyramide; (641)
tert-butyl(2-((1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)amino)pent-
yl)carbamate; (642)
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid-tert-butylester; (643)
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-p-
entane-1,5-diamine ditrifluoroacetic acid; (644)
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid isopropylester; (645)
N-[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-pentyl]-2,2-dimethyl-propionamide; (646)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-tert-butylamide; (647)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid isopropylamide; (648)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid isobutylamide; (649)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(2-methyl-butyl)-amide; (650)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(furan-2-yl-methyl)-amide; (651)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid benzylamide; (652)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(1H-pyrrole-2-yl-methyl)-amide; (653)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-tert-butylamide; (654)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid isopropylamide; (655)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid isobutylamide; (656)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-(2-methyl-butyl)-amide; (657)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-(furan-2-yl-methyl)-amide; (658)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-benzamide; (659)
5-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentanoic
acid isopropylamide; (660)
5-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentanoic
acid isobutylamide; (661)
6-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-hexanoic
acid isopropylamide; and (662)
6-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-hexanoic
acid isobutylamide.
5. A preparation method of the compound represented by formula 1
comprising the following steps, as shown in reaction formula 1
below: preparing the compound represented by formula 4 by reacting
the compound represented by formula 2 with the compound represented
by formula 3 (step 1); and preparing the compound represented by
formula 1 by reacting the compound represented by formula 4
prepared in step 1 above with the compound represented by formula 5
(step 2): ##STR00771## (In reaction formula 1,
R.sup.1.about.R.sup.6, M and X are independently as defined in
formula 1 of claim 1).
6. A preparation method of the compound represented by formula 1
comprising the following steps, as shown in reaction formula 2
below: preparing the compound represented by formula 8 by reacting
the compound represented by formula 7 with the compound represented
by formula 5 (step 1); preparing the compound represented by
formula 9 by reacting the compound represented by formula 8
prepared in step 1 above with hydrazine hydrate (step 2); and
preparing the compound represented by formula 1 by reacting the
compound represented by formula 9 prepared in step 2 above with the
compound represented by formula 3 (step 3): ##STR00772## (In
reaction formula 2, R.sup.1.about.R.sup.6, M and X are
independently as defined in formula 1 of claim 1).
7. A method of treating BET (bromodomain extra-terminal) protein
related disease, the method comprising administering to a subject
in need an effective amount of the compound represented by formula
1, the optical isomer thereof or the pharmaceutically acceptable
salt thereof of claim 1.
8. The method according to claim 7, wherein the BET (bromodomain
extra-terminal) protein related disease is cancer.
9. The method according to claim 8, wherein the cancer is one or
more cancers selected from the group consisting of thymus cancer,
blood cancer, ovarian cancer, cervical cancer, breast cancer,
colorectal cancer, liver cancer, stomach cancer, pancreatic cancer,
colon cancer, peritoneal metastatic cancer, bladder cancer,
prostate cancer, thyroid cancer, lung cancer, osteosarcoma, fibroid
tumor and brain tumor.
10. The method according to claim 7, wherein the BET (bromodomain
extra-terminal) protein related disease is autoimmune disease.
11. The method according to claim 10, wherein the autoimmune
disease is one or more diseases selected from the group consisting
of rheumatoid arthritis, systemic lupus erythematosus, multiple
sclerosis, type 1 diabetes, hyperthyroidism, myasthenia, Crohn's
disease, ankylosing spondylitis, psoriasis, autoimmune malignant
anemia and Sjogren's syndrome.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0001] The present invention relates to a novel
[1,2,4]triazolo[4,3-a]quinoxaline derivative, a method for
preparing the same, and a pharmaceutical composition for preventing
or treating bromodomain extra-terminal (BET) protein-related
diseases including cancer and autoimmune diseases, containing the
same as an active ingredient.
2. Description of the Related Art
[0002] Histone is a basic protein ionically binding to genomic DNA,
which commonly exists in the nucleus of eukaryotic cells from human
and other multicellular organisms to unicellular organisms
represented by Eumycetes (fungus, yeast). In general, histone is
composed of 5 components (H1, H2A, H2B, H3 and H4), and is highly
similar in all species. Genomic DNA is stacked by regular binding
with histone, and the complex of both forms a basic structural unit
called nucleosome. Chromatin structure of chromosome is formed by
the aggregation of the said nucleosome.
[0003] Histone is modified by acetylation, methylation,
phosphorylation, ubiquitination, and sumoylation at the N-terminus
of histone tail. By the modification above, the reactions that
occur in chromosomal DNA such as gene expression, DNA duplication
and DNA repair are controlled by maintaining the chromatin
structure or specifically converting the structure.
[0004] In particular, acetylation of histone is closely related to
the activation of gene transcription. This is because the
modification caused by histone acetylation changes static
electricity, so that the interaction between DNA and histone
octomer becomes loose and thereby transcription is induced
efficiently. In addition to these physical changes, a specific
protein binds to acetylated lysine residues in histone, by which
the protein is involved in gene transcription. Such a specific
protein contains bromodomain.
[0005] Among those proteins containing bromodomain, BET
(bromodomain extra-terminal) family includes the following 4
proteins, BRD2, BRD3, BRD4 and BRDT, 2 bromodomains and 1
extra-terminal domain. The said BET family plays an important role
in immune response and inflammatory response.
[0006] For example, BRD4 protein stimulates NF-.kappa.B (Nuclear
Factor-kappa B) involved in inflammatory response or autoimmunity
to cause auto-immune diseases including rheumatoid arthritis,
systemic lupus erythematosus, multiple sclerosis, type 1 diabetes,
hyperthyroidism, myasthenia, Crohn's disease, ankylosing
spondylitis, psoriasis, autoimmune malignant anemia, Sjogren's
syndrome, and the like.
[0007] Particularly, the NF-.kappa.B protein is a transcription
factor protein regulating various signal transmission systems
involved in inflammatory response, immune function, aging and
tumor. In the absence of external stimuli, it binds to an
inhibitory molecule called I.kappa.B (inhibitory KB), and is
present in the cytoplasm in the inactive state. However, when
external stimuli are present, I.kappa.B is phosphorylated and
inactivated by I.kappa.B kinase (IKK) via intracellular signaling.
Accordingly, NF-.kappa.B separated from I.kappa.B becomes activated
and then moves into the nucleus, and thereby transcription of a
target gene is induced.
[0008] In addition, BET protein has been reported to play an
important role in various types of tumors.
[0009] In particular, BRD4 and BRD3 bind to NUT (nucleoprotein in
testis) in malignant epithelial tumors to form BRD3-NUT or
BRD4-NUT, a novel fusion oncogene, according to the previous
reports. BRD-NUT fusion protein has been reported to prevent cell
differentiation, promote proliferation and contribute to
carcinogenesis (Oncogene 2008, 27, 2237-2242). In addition,
amplification of DNA region containing BRD4 gene was detected in
breast tumor. In the transgenic mice over-expressing BRD2 in B
cells, the development of B cell lymphoma and leukemia was
reported.
[0010] Further, BET protein plays an important role in cell growth
and cell cycle and also relates to viral infection.
[0011] Therefore, the said BET protein has been on the spotlight as
a target for the treatment of various diseases.
SUMMARY OF THE INVENTION
[0012] It is an object of the present invention to provide a novel
[1,2,4]triazolo[4,3-a]quinoxaline derivative, an optical isomer
thereof or a pharmaceutically acceptable salt thereof.
[0013] It is another object of the present invention to provide a
preparation method of the novel [1,2,4]triazolo[4,3-a]quinoxaline
derivative.
[0014] It is also an object of the present invention to provide a
pharmaceutical composition comprising the novel
[1,2,4]triazolo[4,3-a]quinoxaline derivative as an active
ingredient for the prevention or treatment of BET (bromodomain
extra-terminal) protein related diseases.
[0015] To achieve the above objects, according to an aspect of the
present invention, the present invention provides a compound
represented by formula 1 below, an optical isomer thereof or a
pharmaceutically acceptable salt thereof:
##STR00001##
[0016] (In formula 1,
[0017] R.sup.1 is hydrogen, C.sub.1-20 straight or branched alkyl
nonsubstituted or substituted with one or more halogens, or
C.sub.6-20 aryl;
[0018] R.sup.2 is hydrogen, C.sub.1-20 straight or branched alkyl,
or C.sub.1-20 straight or branched alkoxy;
[0019] R.sup.3 is hydrogen, nitro, halogen, nonsubstituted or
substituted C.sub.1-20 straight or branched alkyl, nonsubstituted
or substituted C.sub.1-20 straight or branched alkoxy, 5-10
membered heteroaryl nonsubstituted or substituted with one or more
methyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
##STR00002##
which forms 6 membered cycloalkyl containing one or more
heteroatoms selected from the group consisting of S and O along
with R.sup.4,
[0020] wherein, the substituted C.sub.1-20 straight or branched
alkyl and the substituted C.sub.1-20 straight or branched alkoxy
can be independently substituted with one or more substituents
selected from the group consisting of halogen, C.sub.1-3 straight
or branched alkoxy, 5-10 membered heterocycloalkyl containing one
or more heteroatoms selected from the group consisting of N, O and
S, and C.sub.6-10 aryl nonsubstituted or substituted with one or
more nitro groups,
[0021] A.sup.1 is hydrogen, or C.sub.1-20 straight or branched
alkyl,
[0022] B.sup.1 and B.sup.2 are independently hydrogen, C.sub.1-20
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, or C.sub.6-10
aryl, and B.sup.1 and B.sup.2 are linked to each other to form 5-10
membered heterocycloalkyl nonsubstituted or substituted with one or
more benzyl groups containing one or more heteroatoms selected from
the group consisting of N, O and S,
[0023] C.sup.1 is hydrogen, C.sub.1-20 straight or branched alkyl,
or C.sub.1-20 straight or branched alkoxy,
[0024] D.sup.1 and D.sup.2 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl,
[0025] E.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0026] F.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0027] G.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl;
[0028] R.sup.4 is hydrogen, hydroxy, halogen, nitro, C.sub.1-20
straight or branched alkyl nonsubstituted or substituted with one
or more .dbd.S groups, C.sub.1-20 straight or branched
alkylsulfanyl nonsubstituted or substituted with one or more oxo
(.dbd.O) groups, C.sub.1-20 straight or branched alkylsulfonyl,
5-10 membered heterocycloalkyloxy nonsubstituted or substituted
with one or more C.sub.1-5 straight or branched alkoxycarbonyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, nonsubstituted or substituted 5-10
membered heteroaryl containing one or more heteroatoms selected
from the group consisting of N, O and S, nonsubstituted or
substituted C.sub.1-20 straight or branched alkoxy,
##STR00003##
[0029] wherein, the substituted 5-10 membered heteroaryl can be
substituted with one or more substituents selected from the group
consisting of C.sub.1-3 straight or branched alkyl, C.sub.1-3
straight or branched alkoxy and C.sub.1-3 straight or branched
alkoxy C.sub.1-3 straight or branched alkyl,
[0030] wherein, the substituted C.sub.1-20 straight or branched
alkoxy can be substituted with one or more substituents selected
from the group consisting of halogen, cyano, C.sub.1-3 straight or
branched alkoxy, nonsubstituted or substituted 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, and nonsubstituted or
substituted C.sub.6-10 aryl,
[0031] wherein, the substituted 5-10 membered heterocycloalkyl and
the substituted C.sub.6-10 aryl can be independently substituted
with one or more substituents selected from the group consisting of
cyano,
##STR00004##
C.sub.1-5 straight or branched alkoxycarbonyl, and 5-8 membered
heteroaryl nonsubstituted or substituted with one or more N
groups,
[0032] A.sup.3 is hydrogen, or C.sub.1-20 straight or branched
alkyl,
[0033] B.sup.3 and B.sup.4 are independently hydrogen, C.sub.1-20
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, nonsubstituted or
substituted C.sub.6-10 aryl, nonsubstituted or substituted
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, and B.sup.3
and B.sup.4 are linked to each other to form 5-10 membered
heterocycloalkyl nonsubstituted or substituted with one or more
benzyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0034] wherein, the substituted C.sub.6-10 aryl can be substituted
with one or more substituents selected from the group consisting of
amine, halogen, C.sub.1-5 straight or branched alkyl and C.sub.1-5
straight or branched alkoxy,
[0035] C.sup.3, C.sup.4 and C.sup.5 are independently hydrogen,
amine, halogen, C.sub.1-20 straight or branched alkyl, or
C.sub.1-20 straight or branched alkoxy,
[0036] D.sup.3 and D.sup.4 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens, and
D.sup.3 and D.sup.4 are linked to each other to form 5-10 membered
heteroaryl containing one or more heteroatoms selected from the
group consisting of N, O and S, or 5-10 membered heterocycloalkyl
fused with 5 membered heteroaryl nonsubstituted or substituted with
one or more methyl groups or containing one S group and one or more
heteroatoms selected from the group consisting of N, O and S,
[0037] E.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0038] F.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0039] G.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0040] H.sup.3 is C.sub.6-10 aryl, 5-10 membered heterocycloalkyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, or 5-10 membered heteroaryl
nonsubstituted or substituted with one or more methyl groups
containing one or more heteroatoms selected from the group
consisting of N, O and S,
[0041] I.sup.3 is diC.sub.1-3 straight or branched alkylamino;
[0042] R.sup.5 is hydrogen, halogen, C.sub.1-20 straight or
branched alkyl nonsubstituted or substituted with one or more
halogens, or C.sub.1-20 straight or branched alkoxy;
[0043] R.sup.6 is hydroxy,
##STR00005##
[0044] B.sup.5 and B.sup.6 are independently hydrogen, C.sub.1-20
straight or branched alkyl, C.sub.6-10 aryl C.sub.1-3 straight or
branched alkyl, or 5-10 membered heteroaryl C.sub.1-3 straight or
branched alkyl containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0045] D.sup.5 and D.sup.6 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens,
[0046] E.sup.5 is C.sub.1-20 straight or branched alkyl saturated
or containing one or more carbon.ident.carbon unsaturated bonds,
C.sub.1-20 straight or branched alkoxy saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.3-10
cycloalkyloxy, C.sub.3-10 cycloalkyl C.sub.1-3 straight or branched
alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryloxy, C.sub.6-10 aryl
C.sub.1-3 straight or branched alkoxy, C.sub.1-20 straight or
branched alkylsulfanyl, nonsubstituted or substituted C.sub.6-10
aryl, diC.sub.1-3 straight or branched alkylamino, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or nonsubstituted or
substituted 5-10 membered heteroaryl containing one or more N
groups,
[0047] wherein, the substituted C.sub.1-20 straight or branched
alkyl can be substituted with one or more substituents selected
from the group consisting of hydroxy, halogen, C.sub.1-3 straight
or branched alkoxy, C.sub.1-3 straight or branched
alkylcarbonyloxy, C.sub.1-3 straight or branched alkoxycarbonyl,
hydroxycarbonyl, C.sub.6-10 aryl nonsubstituted or substituted with
one or more hydroxyl groups, 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, and
##STR00006##
[0048] T.sup.1 and T.sup.2 are independently hydrogen, C.sub.1-5
straight or branched alkyl, C.sub.1-5 straight or branched
alkoxycarbonyl, C.sub.1-5 straight or branched alkylcarbonyl
nonsubstituted or substituted with one or more halogens or hydroxyl
groups, and T.sup.1 and T.sup.2 are linked to each other to form
heterocycloalkyl nonsubstituted or substituted with one or more
hydroxyl groups or C.sub.1-3 straight or branched alkyl groups
containing one S group and one or more heteroatoms selected from
the group consisting of N, O and S,
[0049] wherein, the substituted C.sub.6-10 aryl and the substituted
5-10 membered heteroaryl can be independently substituted with one
or more substituents selected from the group consisting of halogen,
nitro, C.sub.1-5 straight or branched alkyl and C.sub.1-5 straight
or branched alkoxy,
[0050] F.sup.5 is C.sub.1-20 straight or branched alkyl, C.sub.3-10
cycloalkyl, or C.sub.6-10 aryl nonsubstituted or substituted with
one or more halogens,
[0051] G.sup.5 is C.sub.1-20 straight or branched alkyl,
[0052] H.sup.5 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl nonsubstituted or substituted with one or more
halogens;
[0053] M is C.sub.1-20 straight or branched alkylene; and
[0054] X is --NH--, or --O--).
[0055] According to another aspect of the present invention, the
present invention also provides a preparation method of the
compound represented by formula 1 comprising the following steps,
as shown in reaction formula 1 below:
[0056] preparing the compound represented by formula 4 by reacting
the compound represented by formula 2 with the compound represented
by formula 3 (step 1); and
[0057] preparing the compound represented by formula 1 by reacting
the compound represented by formula 4 prepared in step 1 above with
the compound represented by formula 5 (step 2):
##STR00007##
[0058] (In reaction formula 1,
[0059] R.sup.1.about.R.sup.6, M and X are independently as defined
in formula 1 above)
[0060] According to another aspect of the present invention, the
present invention also provides a preparation method of the
compound represented by formula 1 comprising the following steps,
as shown in reaction formula 2 below:
[0061] preparing the compound represented by formula 8 by reacting
the compound represented by formula 7 with the compound represented
by formula 5 (step 1);
[0062] preparing the compound represented by formula 9 by reacting
the compound represented by formula 8 prepared in step 1 above with
hydrazine hydrate (step 2); and
[0063] preparing the compound represented by formula 1 by reacting
the compound represented by formula 9 prepared in step 2 above with
the compound represented by formula 3 (step 3):
##STR00008##
[0064] (In reaction formula 2,
[0065] R.sup.1.about.R.sup.6, M and X are independently as defined
in formula 1 above).
[0066] According to another aspect of the present invention, the
present invention provides a pharmaceutical composition comprising
the compound represented by formula 1, the optical isomer thereof
or the pharmaceutically acceptable salt thereof as an active
ingredient for the prevention or treatment of BET (bromodomain
extra-terminal) protein related diseases.
[0067] According to another aspect of the present invention, the
present invention provides a method for preventing, ameliorating or
treating BET (bromodomain extra-terminal) protein related diseases
which comprises a step of administering the pharmaceutical
composition comprising the compound represented by formula 1, the
optical isomer thereof or the pharmaceutically acceptable salt
thereof as an active ingredient to a subject.
[0068] In addition, according to another aspect of the present
invention, the present invention provides a use of the
pharmaceutical composition comprising the compound represented by
formula 1, the optical isomer thereof or the pharmaceutically
acceptable salt thereof as an active ingredient.
Advantageous Effect
[0069] The novel [1,2,4]triazolo[4,3-a]quinoxaline derivative
provided in an aspect of the present invention, inhibits the
binding of BRD4, one of BET protein family, at a low concentration,
and displays excellent cytotoxicity in tumor cells, so that it can
be used as a pharmaceutical composition for the prevention or
treatment of BET protein related diseases including cancer and
autoimmune disease.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0070] Hereinafter, the present invention is described in
detail.
[0071] In an aspect of the present invention, the present invention
provides a compound represented by formula 1, an optical isomer
thereof or a pharmaceutically acceptable salt thereof:
##STR00009##
[0072] (In formula 1,
[0073] R.sup.1 is hydrogen, C.sub.1-20 straight or branched alkyl
nonsubstituted or substituted with one or more halogens, or
C.sub.6-20 aryl;
[0074] R.sup.2 is hydrogen, C.sub.1-20 straight or branched alkyl,
or C.sub.1-20 straight or branched alkoxy;
[0075] R.sup.3 is hydrogen, nitro, halogen, nonsubstituted or
substituted C.sub.1-20 straight or branched alkyl, nonsubstituted
or substituted C.sub.1-20 straight or branched alkoxy, 5-10
membered heteroaryl nonsubstituted or substituted with one or more
methyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
##STR00010##
which forms 6 membered cycloalkyl containing one or more
heteroatoms selected from the group consisting of S and O along
with R.sup.4,
[0076] wherein, the substituted C.sub.1-20 straight or branched
alkyl and the substituted C.sub.1-20 straight or branched alkoxy
can be independently substituted with one or more substituents
selected from the group consisting of halogen, C.sub.1-3 straight
or branched alkoxy, 5-10 membered heterocycloalkyl containing one
or more heteroatoms selected from the group consisting of N, O and
S, and C.sub.6-10 aryl nonsubstituted or substituted with one or
more nitro groups,
[0077] A.sup.1 is hydrogen, or C.sub.1-20 straight or branched
alkyl,
[0078] B.sup.1 and B.sup.2 are independently hydrogen, C.sub.1-20
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, or C.sub.6-10
aryl, and B.sup.1 and B.sup.2 are linked to each other to form 5-10
membered heterocycloalkyl nonsubstituted or substituted with one or
more benzyl groups containing one or more heteroatoms selected from
the group consisting of N, O and S,
[0079] C.sup.1 is hydrogen, C.sub.1-20 straight or branched alkyl,
or C.sub.1-20 straight or branched alkoxy,
[0080] D.sup.1 and D.sup.2 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl,
[0081] E.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0082] F.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0083] G.sup.1 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl;
[0084] R.sup.4 is hydrogen, hydroxy, halogen, nitro, C.sub.1-20
straight or branched alkyl nonsubstituted or substituted with one
or more .dbd.S groups, C.sub.1-20 straight or branched
alkylsulfanyl nonsubstituted or substituted with one or more oxo
(.dbd.O) groups, C.sub.1-20 straight or branched alkylsulfonyl,
5-10 membered heterocycloalkyloxy nonsubstituted or substituted
with one or more C.sub.1-5 straight or branched alkoxycarbonyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, nonsubstituted or substituted 5-10
membered heteroaryl containing one or more heteroatoms selected
from the group consisting of N, O and S, nonsubstituted or
substituted C.sub.1-20 straight or branched alkoxy,
##STR00011##
[0085] wherein, the substituted 5-10 membered heteroaryl can be
substituted with one or more substituents selected from the group
consisting of C.sub.1-3 straight or branched alkyl, C.sub.1-3
straight or branched alkoxy and C.sub.1-3 straight or branched
alkoxy C.sub.1-3 straight or branched alkyl,
[0086] wherein, the substituted C.sub.1-20 straight or branched
alkoxy can be substituted with one or more substituents selected
from the group consisting of halogen, cyano, C.sub.1-3 straight or
branched alkoxy, nonsubstituted or substituted 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, and nonsubstituted or
substituted C.sub.6-10 aryl,
[0087] wherein, the substituted 5-10 membered heterocycloalkyl and
the substituted C.sub.6-10 aryl can be independently substituted
with one or more substituents selected from the group consisting of
cyano,
##STR00012##
C.sub.1-5 straight or branched alkoxycarbonyl, and 5-8 membered
heteroaryl nonsubstituted or substituted with one or more N
groups,
[0088] A.sup.3 is hydrogen, or C.sub.1-20 straight or branched
alkyl,
[0089] B.sup.3 and B.sup.4 are independently hydrogen, C.sub.1-20
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, nonsubstituted or
substituted C.sub.6-10 aryl, nonsubstituted or substituted
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, and B.sup.3
and B.sup.4 are linked to each other to form 5-10 membered
heterocycloalkyl nonsubstituted or substituted with one or more
benzyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0090] wherein, the substituted C.sub.6-10 aryl can be substituted
with one or more substituents selected from the group consisting of
amine, halogen, C.sub.1-5 straight or branched alkyl and C.sub.1-5
straight or branched alkoxy,
[0091] C.sup.3, C.sup.4 and C.sup.5 are independently hydrogen,
amine, halogen, C.sub.1-20 straight or branched alkyl, or
C.sub.1-20 straight or branched alkoxy,
[0092] D.sup.3 and D.sup.4 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens, and
D.sup.3 and D.sup.4 are linked to each other to form 5-10 membered
heteroaryl containing one or more heteroatoms selected from the
group consisting of N, O and S, or 5-10 membered heterocycloalkyl
fused with 5 membered heteroaryl nonsubstituted or substituted with
one or more methyl groups or containing one S group and one or more
heteroatoms selected from the group consisting of N, O and S,
[0093] E.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0094] F.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0095] G.sup.3 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl,
[0096] H.sup.3 is C.sub.6-10 aryl, 5-10 membered heterocycloalkyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, or 5-10 membered heteroaryl
nonsubstituted or substituted with one or more methyl groups
containing one or more heteroatoms selected from the group
consisting of N, O and S,
[0097] I.sup.3 is diC.sub.1-3 straight or branched alkylamino;
[0098] R.sup.5 is hydrogen, halogen, C.sub.1-20 straight or
branched alkyl nonsubstituted or substituted with one or more
halogens, or C.sub.1-20 straight or branched alkoxy;
[0099] R.sup.6 is hydroxy,
##STR00013##
[0100] B.sup.5 and B.sup.6 are independently hydrogen, C.sub.1-20
straight or branched alkyl, C.sub.6-10 aryl C.sub.1-3 straight or
branched alkyl, or 5-10 membered heteroaryl C.sub.1-3 straight or
branched alkyl containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0101] D.sup.5 and D.sup.6 are independently hydrogen, hydroxy,
C.sub.1-20 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-20 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-20 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens,
[0102] E.sup.5 is C.sub.1-20 straight or branched alkyl saturated
or containing one or more carbon.ident.carbon unsaturated bonds,
C.sub.1-20 straight or branched alkoxy saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.3-10
cycloalkyloxy, C.sub.3-10 cycloalkyl C.sub.1-3 straight or branched
alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryloxy, C.sub.6-10 aryl
C.sub.1-3 straight or branched alkoxy, C.sub.1-20 straight or
branched alkylsulfanyl, nonsubstituted or substituted C.sub.6 10
aryl, diC.sub.1-3 straight or branched alkylamino, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or nonsubstituted or
substituted 5-10 membered heteroaryl containing one or more N
groups,
[0103] wherein, the substituted C.sub.1-20 straight or branched
alkyl can be substituted with one or more substituents selected
from the group consisting of hydroxy, halogen, C.sub.1-3 straight
or branched alkoxy, C.sub.1-3 straight or branched
alkylcarbonyloxy, C.sub.1-3 straight or branched alkoxycarbonyl,
hydroxycarbonyl, C.sub.6-10 aryl nonsubstituted or substituted with
one or more hydroxyl groups, 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, and
##STR00014##
[0104] T.sup.1 and T.sup.2 are independently hydrogen, C.sub.1-5
straight or branched alkyl, C.sub.1-5 straight or branched
alkoxycarbonyl, C.sub.1-5 straight or branched alkylcarbonyl
nonsubstituted or substituted with one or more halogens or hydroxyl
groups, and T.sup.1 and T.sup.2 are linked to each other to form
heterocycloalkyl nonsubstituted or substituted with one or more
hydroxyl groups or C.sub.1-3 straight or branched alkyl groups
containing one S group and one or more heteroatoms selected from
the group consisting of N, O and S,
[0105] wherein, the substituted C.sub.6-10 aryl and the substituted
5-10 membered heteroaryl can be independently substituted with one
or more substituents selected from the group consisting of halogen,
nitro, C.sub.1-5 straight or branched alkyl and C.sub.1-5 straight
or branched alkoxy,
[0106] F.sup.5 is C.sub.1-20 straight or branched alkyl, C.sub.3-10
cycloalkyl, or C.sub.6-10 aryl nonsubstituted or substituted with
one or more halogens,
[0107] G.sup.5 is C.sub.1-20 straight or branched alkyl,
[0108] H.sup.5 is C.sub.1-20 straight or branched alkyl, or
C.sub.6-10 aryl nonsubstituted or substituted with one or more
halogens;
[0109] M is C.sub.1-20 straight or branched alkylene; and
[0110] X is --NH--, or --O--).
[0111] Preferable examples of the substituent according to formula
1 above are as follows:
[0112] The compound, the optical isomer thereof or the
pharmaceutically acceptable salt thereof wherein:
[0113] R.sup.1 is hydrogen, C.sub.1-10 straight or branched alkyl
nonsubstituted or substituted with one or more halogens, or
C.sub.6-10 aryl;
[0114] R.sup.2 is hydrogen, C.sub.1-10 straight or branched alkyl,
or C.sub.1-10 straight or branched alkoxy;
[0115] R.sup.3 is hydrogen, nitro, halogen, nonsubstituted or
substituted C.sub.1-10 straight or branched alkyl, nonsubstituted
or substituted C.sub.1-10 straight or branched alkoxy, 5-10
membered heteroaryl nonsubstituted or substituted with one or more
methyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
##STR00015##
which forms 6 membered cycloalkyl containing one or more
heteroatoms selected from the group consisting of S and O along
with R.sup.4,
[0116] wherein, the substituted C.sub.1-10 straight or branched
alkyl and the substituted C.sub.1-10 straight or branched alkoxy
can be independently substituted with one or more substituents
selected from the group consisting of halogen, C.sub.1-3 straight
or branched alkoxy, 5-10 membered heterocycloalkyl containing one
or more heteroatoms selected from the group consisting of N, O and
S, and C.sub.6 aryl nonsubstituted or substituted with one or more
nitro groups,
[0117] A.sup.1 is hydrogen, or C.sub.1-10 straight or branched
alkyl,
[0118] B.sup.1 and B.sup.2 are independently hydrogen, C.sub.1-10
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, or C.sub.6-10
aryl, and B.sup.1 and B.sup.2 are linked to each other to form 5-10
membered heterocycloalkyl nonsubstituted or substituted with one or
more benzyl groups containing one or more heteroatoms selected from
the group consisting of N, O and S,
[0119] C.sup.1 is hydrogen, C.sub.1-10 straight or branched alkyl,
or C.sub.1-10 straight or branched alkoxy,
[0120] D.sup.1 and D.sup.2 are independently hydrogen, hydroxy,
C.sub.1-10 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-10 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-10 straight or branched alkylsulfonyl,
[0121] E.sup.1 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0122] F.sup.1 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl,
[0123] G.sup.1 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl;
[0124] R.sup.4 is hydrogen, hydroxy, halogen, nitro, C.sub.1-10
straight or branched alkyl nonsubstituted or substituted with one
or more .dbd.S groups, C.sub.1-10 straight or branched
alkylsulfanyl nonsubstituted or substituted with one or more oxo
(.dbd.O) groups, C.sub.1-10 straight or branched alkylsulfonyl,
5-10 membered heterocycloalkyloxy nonsubstituted or substituted
with one or more C.sub.1-5 straight or branched alkoxycarbonyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, nonsubstituted or substituted 5-10
membered heteroaryl containing one or more heteroatoms selected
from the group consisting of N, O and S, nonsubstituted or
substituted C.sub.1-10 straight or branched alkoxy,
##STR00016##
[0125] wherein, the substituted 5-10 membered heteroaryl can be
substituted with one or more substituents selected from the group
consisting of C.sub.1-3 straight or branched alkyl, C.sub.1-3
straight or branched alkoxy and C.sub.1-3 straight or branched
alkoxy C.sub.1-3 straight or branched alkyl,
[0126] wherein, the substituted C.sub.1-10 straight or branched
alkoxy can be substituted with one or more substituents selected
from the group consisting of halogen, cyano, C.sub.1-3 straight or
branched alkoxy, nonsubstituted or substituted 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, and nonsubstituted or
substituted C.sub.6-10 aryl,
[0127] wherein, the substituted 5-10 membered heterocycloalkyl and
the substituted C.sub.6 10 aryl can be independently substituted
with one or more substituents selected from the group consisting of
cyano,
##STR00017##
C.sub.1-5 straight or branched alkoxycarbonyl, and 5-8 membered
heteroaryl nonsubstituted or substituted with one or more N
groups,
[0128] A.sup.3 is hydrogen, or C.sub.1-10 straight or branched
alkyl,
[0129] B.sup.3 and B.sup.4 are independently hydrogen, C.sub.1-10
straight or branched alkyl, diC.sub.1-3 straight or branched
alkylamino C.sub.1-3 straight or branched alkyl, nonsubstituted or
substituted C.sub.6-10 aryl, nonsubstituted or substituted
C.sub.6-10 aryl C.sub.1-3 straight or branched alkyl, and B.sup.3
and B.sup.4 are linked to each other to form 5-10 membered
heterocycloalkyl nonsubstituted or substituted with one or more
benzyl groups containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0130] wherein, the substituted C.sub.6-10 aryl can be substituted
with one or more substituents selected from the group consisting of
amine, halogen, C.sub.1-5 straight or branched alkyl and C.sub.1-5
straight or branched alkoxy,
[0131] C.sup.3, C.sup.4 and C.sup.5 are independently hydrogen,
amine, halogen, C.sub.1-10 straight or branched alkyl, or
C.sub.1-10 straight or branched alkoxy,
[0132] D.sup.3 and D.sup.4 are independently hydrogen, hydroxy,
C.sub.1-10 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-10 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-10 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens, and
D.sup.3 and D.sup.4 are linked to each other to form 5-10 membered
heteroaryl containing one or more heteroatoms selected from the
group consisting of N, O and S, or 5-10 membered heterocycloalkyl
fused with 5 membered heteroaryl nonsubstituted or substituted with
one or more methyl groups or containing one S group and one or more
heteroatoms selected from the group consisting of N, O and S,
[0133] E.sup.3 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl C.sub.1-5 straight or branched alkyl,
[0134] F.sup.3 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl,
[0135] G.sup.3 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl,
[0136] H.sup.3 is C.sub.6-10 aryl, 5-10 membered heterocycloalkyl
containing one or more heteroatoms selected from the group
consisting of N, O and S, or 5-10 membered heteroaryl
nonsubstituted or substituted with one or more methyl groups
containing one or more heteroatoms selected from the group
consisting of N, O and S,
[0137] I.sup.3 is diC.sub.1-3 straight or branched alkylamino;
[0138] R.sup.5 is hydrogen, halogen, C.sub.1-10 straight or
branched alkyl nonsubstituted or substituted with one or more
halogens, or C.sub.1-10 straight or branched alkoxy;
[0139] R.sup.6 is hydroxy,
##STR00018##
[0140] B.sup.5 and B.sup.6 are independently hydrogen, C.sub.1-10
straight or branched alkyl, C.sub.6-10 aryl C.sub.1-3 straight or
branched alkyl, or 5-10 membered heteroaryl C.sub.1-3 straight or
branched alkyl containing one or more heteroatoms selected from the
group consisting of N, O and S,
[0141] D.sup.5 and D.sup.6 are independently hydrogen, hydroxy,
C.sub.1-10 straight or branched alkyl saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.1-10 straight
or branched alkyl nonsubstituted or substituted with one or more
cyano groups, or C.sub.1-10 straight or branched alkylsulfonyl
nonsubstituted or substituted with one or more halogens,
[0142] E.sup.5 is C.sub.1-10 straight or branched alkyl saturated
or containing one or more carbon.ident.carbon unsaturated bonds,
C.sub.1-10 straight or branched alkoxy saturated or containing one
or more carbon.ident.carbon unsaturated bonds, C.sub.3-10
cycloalkyloxy, C.sub.3-10 cycloalkyl C.sub.1-3 straight or branched
alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryloxy, C.sub.6-10 aryl
C.sub.1-3 straight or branched alkoxy, C.sub.1-10 straight or
branched alkylsulfanyl, nonsubstituted or substituted C.sub.6-10
aryl, diC.sub.1-3 straight or branched alkylamino, 5-10 membered
heterocycloalkyl containing one or more heteroatoms selected from
the group consisting of N, O and S, or nonsubstituted or
substituted 5-10 membered heteroaryl containing one or more N
groups,
[0143] wherein, the substituted C.sub.1-10 straight or branched
alkyl can be substituted with one or more substituents selected
from the group consisting of hydroxy, halogen, C.sub.1-3 straight
or branched alkoxy, C.sub.1-3 straight or branched
alkylcarbonyloxy, C.sub.1-3 straight or branched alkoxycarbonyl,
hydroxycarbonyl, C.sub.6-10 aryl nonsubstituted or substituted with
one or more hydroxyl groups, 5-10 membered heteroaryl containing
one or more heteroatoms selected from the group consisting of N, O
and S, and
##STR00019##
[0144] T.sup.1 and T.sup.2 are independently hydrogen, C.sub.1-5
straight or branched alkyl, C.sub.1-5 straight or branched
alkoxycarbonyl, C.sub.1-5 straight or branched alkylcarbonyl
nonsubstituted or substituted with one or more halogens or hydroxyl
groups, and T.sup.1 and T.sup.2 are linked to each other to form
heterocycloalkyl nonsubstituted or substituted with one or more
hydroxyl groups or C.sub.1-3 straight or branched alkyl groups
containing one S group and one or more heteroatoms selected from
the group consisting of N, O and S,
[0145] wherein, the substituted C.sub.6-10 aryl and the substituted
5-10 membered heteroaryl can be independently substituted with one
or more substituents selected from the group consisting of halogen,
nitro, C.sub.1-5 straight or branched alkyl and C.sub.1-5 straight
or branched alkoxy,
[0146] F.sup.5 is C.sub.1-10 straight or branched alkyl, C.sub.3-10
cycloalkyl, or C.sub.6 10 aryl nonsubstituted or substituted with
one or more halogens,
[0147] G.sup.5 is C.sub.1-10 straight or branched alkyl,
[0148] H.sup.5 is C.sub.1-10 straight or branched alkyl, or
C.sub.6-10 aryl nonsubstituted or substituted with one or more
halogens;
[0149] M is C.sub.1-10 straight or branched alkylene; and
[0150] X is --NH--, or --O--.
[0151] More preferable examples of the substituent according to
formula 1 above are as follows:
[0152] The compound, the optical isomer thereof or the
pharmaceutically acceptable salt thereof wherein:
[0153] R.sup.1 is --H, --CH.sub.3, --CH.sub.2CH.sub.3,
--CF.sub.3,
##STR00020##
[0154] R.sup.2 is --H, --CH.sub.3, or --OCH.sub.3;
[0155] R.sup.3 is --H, --Cl, --F, --CH.sub.3, --CF.sub.3,
--OCH.sub.3, --OCF.sub.3, --NO.sub.2, --NH.sub.2,
##STR00021## ##STR00022##
which forms
##STR00023##
along with R.sup.4;
[0156] R.sup.4 is --H, --OH, --Cl, --F, --CH.sub.3, --OCH.sub.3,
--SCH.sub.3, --OCF.sub.3, --NO.sub.2, --NH.sub.2,
##STR00024## ##STR00025## ##STR00026##
[0157] R.sup.5 is --H, --Cl, --CH.sub.3, --CF.sub.3, or
--OCH.sub.3;
[0158] R.sup.6 is --NH.sub.2, hydroxy,
##STR00027## ##STR00028## ##STR00029## ##STR00030## ##STR00031##
##STR00032##
[0159] M is C.sub.3-4 straight or branched alkylene; and
[0160] X is --NH--, or --O--.
[0161] Most preferable examples of the substituent according to
formula 1 above are as follows: [0162] (1)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; [0163] (2)
N.sup.1-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diam-
ine dihydrochloride; [0164] (3)
2,2-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-propionamide; [0165] (4)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid isopropylester; [0166] (5)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-acetamid-
e; [0167] (6)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-isobutyr-
amide; [0168] (7)
3-methyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-butyramide; [0169] (8)
3,3-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-butyramide; [0170] (9)
2-(R)-hydroxy-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0171] (10)
2-(S)-hydroxy-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0172] (11)
N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-benzam-
ide; [0173] (12)
2-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; [0174] (13)
2,6-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; [0175] (14)
4-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; [0176] (15)
3-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; [0177] (16)
3,4-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; [0178] (17)
2,3-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; [0179] (18)
3,5-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; [0180] (19)
2,6-dichloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-nicotinamide; [0181] (20)
6-chloro-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-nicotinamide; [0182] (21)
2-chloro-6-methyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-nicotinamide; [0183] (22)
1-tert-butyl-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-urea; [0184] (23)
1-(4-fluoro-phenyl)-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-urea; [0185] (24)
1-(3-fluoro-phenyl)-3-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-urea; [0186] (25)
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid benzylester; [0187] (26)
[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; [0188] (27)
N.sup.1-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)but-
ane-1,4-diamine ditrifluoroacetic acid; [0189] (28)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2,2-dimethyl-propionamide; [0190] (29)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-isobutyramide; [0191] (30)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; [0192] (31)
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-benzamide; [0193] (32)
2-chloro-N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-benzamide; [0194] (33)
6-chloro-N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-nicotinamide; [0195] (34)
[4-(1,7,8-trimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-c-
arbamic acid-tert-butylester; [0196] (35)
[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; [0197] (36)
N.sup.1-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; [0198] (37)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; [0199] (38)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(R)-hydroxy-3-methyl-butyramide; [0200] (39)
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(S)-hydroxy-3-methyl-butyramide; [0201] (40)
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carb-
amic acid-tert-butylester; [0202] (41)
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butane]-1,4-
-diamine dihydrochloride; [0203] (42)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-2,-
2-dimethyl-propionamide; [0204] (43)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-is-
obutyramide; [0205] (44)
1-tert-butyl-3-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-urea; [0206] (45)
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-be-
nzamide; [0207] (46)
1-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-3--
phenyl-urea; [0208] (47)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0209] (48)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-1,4-diamine dihydrochloride; [0210] (49)
N-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-2,2-dimethyl-propionamide; [0211] (50)
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-isobutyramide; [0212] (51)
N-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; [0213] (52)
1-tert-butyl-3-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-urea; [0214] (53)
1-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-3-phenyl-urea; [0215] (54)
[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0216] (55)
N.sup.1-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)butane--
1,4-diamine hydrochloride; [0217] (56)
N-[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide; [0218] (57)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0219] (58)
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; [0220] (59)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; [0221] (60)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0222] (61)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid ethylester; [0223] (62)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; [0224] (63)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-sec-butylester; [0225] (64)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid propylester; [0226] (65)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid allylester; [0227] (66)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid cyclopentylester; [0228] (67)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid phenylester; [0229] (68)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid benzylester; [0230] (69)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-acetamide; [0231] (70)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-isobutyramide; [0232] (71) 3-methyl-buten-2-oic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0233] (72) butene-2-oic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0234] (73) 3-methyl-pentanoic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0235] (74)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0236] (75)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3,3-dimethyl-butyramide; [0237] (76) cyclopropanecarboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0238] (77)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methyl-butyramide; [0239] (78)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-ethyl-butyramide; [0240] (79) 4-methyl-pentanoic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0241] (80)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methoxy-acetamide; [0242] (81)
3-cyclopentyl-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-propionamide; [0243] (82)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-(R)-hydroxy-3-methyl-butyramide; [0244] (83)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-(S)-hydroxy-3-methyl-butyramide; [0245] (84)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-thiophene-2-yl-acetamide; [0246] (85)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-furan-2-yl-acetamide; [0247] (86)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-phenyl-acetamide; [0248] (87) acetic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamoyl]-methylester; [0249] (88)
1-tert-butyl-3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-urea; [0250] (89)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-ethyl-urea; [0251] (90)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-3-isopropyl-urea; [0252] (91)
3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-1,1-dimethyl-urea; [0253] (92) morpholine-4-carboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0254] (93)
1-cyclohexyl-3-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-urea; [0255] (94)
1-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-phenyl-urea; [0256] (95)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide; [0257] (96)
4-tert-butyl-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-benzamide; [0258] (97)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-methoxy-benzamide; [0259] (98)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-4-fluoro-benzamide; [0260] (99)
2-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0261] (100)
4-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0262] (101)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-4-nitro-benzamide; [0263] (102)
2,3-dichloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-benzamide; [0264] (103)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-isonicotinamide; [0265] (104)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-nicotinamide; [0266] (105) pyridine-2-carboxylic
acid-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-amide; [0267] (106)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2-fluoro-benzamide; [0268] (107)
6-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-nicotinamide; [0269] (108)
2-chloro-N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; [0270] (109)
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-methanesulfonamide; [0271] (110)
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-thiocarbamic acid-S-isopropylester; [0272] (111)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid-tert-butylester; [0273] (112)
N.sup.1-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl)-butane-1,4-diamine dihydrochloride; [0274] (113)
N-[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-2,2-dimethyl-propionamide; [0275] (114)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid isopropylester; [0276] (115)
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid isobutylester; [0277] (116)
N-[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-3,3-dimethyl-butyramide; [0278] (117)
[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; [0279] (118)
N.sup.1-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine dihydrochloride; [0280] (119)
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; [0281] (120)
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid isobutylester; [0282] (121)
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; [0283] (122)
N.sup.1-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid; [0284] (123)
N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; [0285] (124)
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3,3-dimethyl-butyramide; [0286] (125)
2-(R)-hydroxy-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0287] (126)
2-(S)-hydroxy-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0288] (127)
N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-benzamide; [0289] (128)
2-chloro-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; [0290] (129)
2-chloro-N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-6-methyl-nicotinamide; [0291] (130)
{4-[6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-b-
utyl}-carbamic acid-tert-butylester; [0292] (131)
N.sup.1-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid;
[0293] (132)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; [0294] (133)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0295] (134)
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; [0296] (135)
N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0297] (136)
2-(R)-hydroxy-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0298] (137)
2-(S)-hydroxy-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0299] (138)
N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide; [0300] (139)
2-fluoro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0301] (140)
2-chloro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0302] (141)
2-chloro-N-[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; [0303] (142)
[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid-tert-butylester; [0304] (143)
N.sup.1-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; [0305]
(144)
[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isopropylester; [0306] (145)
N-[4-(6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0307] (146)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0308] (147)
N.sup.1-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; [0309] (148)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; [0310] (149)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0311] (150)
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; [0312] (151)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0313] (152)
2-(R)-hydroxy-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0314] (153)
2-(S)-hydroxy-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0315] (154)
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-benzamide; [0316] (155)
2-fluoro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0317] (156)
2-chloro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-benzamide; [0318] (157)
2-chloro-N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-6-methyl-nicotinamide; [0319] (158)
[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0320] (159)
N.sup.1-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine difluoroacetic acid; [0321] (160)
N-[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0322] (161)
[4-(8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0323] (162)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0324] (163)
N.sup.1-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0325] (164)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2,2-dimethyl-propionamide; [0326] (165)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid isopropylester; [0327] (166)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; [0328] (167)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3,3-dimethyl-butyramide; [0329] (168)
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid isobutylester; [0330] (169)
1-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-tert-butyl-urea; [0331] (170)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-benzamide; [0332] (171)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-chloro-benzamide; [0333] (172)
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-chloro-6-methyl-nicotinamide; [0334] (173)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl-carbamic acid-tert-butylester; [0335] (174)
N.sup.1-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; [0336] (175)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; [0337] (176)
[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; [0338] (177)
N-[4-(7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl-3-methyl-butyramide; [0339] (178)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid-tert-butylester; [0340] (179)
N.sup.1-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; [0341]
(180)
2,2-dimethyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyc-
lopenta[a]anthracene-4-ylamino)-butyl]-propionamide; [0342] (181)
3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclope-
nta[a]anthracene-4-ylamino)-butyl]-butyramide; [0343] (182)
2-(R)-hydroxy-3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-te-
traaza-cyclopenta[a]anthracene-4-ylamino)-butyl]-butyramide; [0344]
(183)
2-(S)-hydroxy-3-methyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-te-
traaza-cyclopenta[a]anthracene-4-ylamino)-butyl]-butyramide; [0345]
(184) acetic
acid-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclop-
enta[a]anthracene-4-ylamino)-butyl]-carbamoyl]-methylester; [0346]
(185)
N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]ant-
hracene-4-ylamino)-butyl]-2-thiophene-2-yl-acetamide; [0347] (186)
N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]ant-
hracene-4-ylamino)-butyl]-benzamide; [0348] (187)
2-chloro-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclope-
nta[a]anthracene-4-ylamino)-butyl]-benzamide; [0349] (188)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid isopropylester; [0350] (189)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid isobutylester; [0351] (190)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid cyclopentylester; [0352]
(191)
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid phenylester; [0353] (192)
1-isopropyl-3-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cycl-
openta[a]anthracene-4-ylamino)-butyl]-urea; [0354] (193)
[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; [0355] (194)
N.sup.1-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; [0356] (195)
3-methyl-N-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; [0357] (196) 3-methyl-pentanoic
acid-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; [0358] (197)
4-(4-tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-7-carboxylic acid methylester; [0359] (198)
4-(4-amino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carbo-
xylic acid methylester ditrifluoroacetic acid; [0360] (199)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid methylester; [0361] (200)
4-[(4-tert-butoxycarbamoylamino)-butylamino]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-7-carboxylic acid; [0362] (201)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid; [0363] (202)
[4-(7-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester; [0364] (203)
[4-(7-tert-butylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-carbamic acid-tert-butylester; [0365] (204)
4-(4-isobutyramido-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-7-carboxylic acid isopropylamide; [0366] (205)
4-(4-benzoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
7-carboxylic acid isopropylamide; [0367] (206)
{4-[7-(2-dimethylamino-ethylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0368]
(207)
4-(4-benzoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
7-carboxylic acid-(2-dimethylamino-ethyl)-amide; [0369] (208)
N-{4-[7-(4-benzyl-piperazine-1-carbonyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-benzamide; [0370] (209)
N-{4-[1-methyl-7-(piperazine-1-carbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-benzamide; [0371] (210)
[4-(7-benzylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; [0372] (211)
{4-[7-(4-chloro-benzylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0373] (212)
[4-(1-methyl-7-phenylcarbamoyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; [0374] (213)
{4-[7-(2-amino-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0375] (214)
{4-[7-(2-amino-4-methyl-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0376]
(215)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-phenyl)-amide; [0377] (216)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-4-methyl-phenyl)-amide;
[0378] (217)
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid-(2-amino-4,5-dimethoxy-phenyl)-amide;
[0379] (218)
{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0380]
(219)
{4-[1-methyl-7-(5-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0381]
(220)
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0382]
(221)
N.sup.1-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid;
[0383] (222)
3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]-
triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0384]
(223)
3-methyl-N-{4-[1-methyl-7-(5-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0385] (224)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; [0386] (225)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; [0387]
(226)
N-{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; [0388]
(227)
N-{4-[7-(5,6-dimethoxy-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0389]
(228)
{4-[1-methyl-7-(1-methyl-H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-carbamic acid propylester; [0390] (229)
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid cyclopentylester; [0391]
(230)
2,2-dimethyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-propionamide; [0392]
(231) acetic
acid-1-{4-[7-(1-methyl-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]tri-
azolo[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-1-methyl-ethylester;
[0393] (232)
2-hydroxy-N-{4-(7-(1-methyl-1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino)-butyl}-2-methyl-propionamide;
[0394] (233)
2,2-difluoro-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,-
2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0395]
(234)
2-(S)-hydroxy-3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-
-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide;
[0396] (235)
2-(R)-hydroxy-3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzimidazole--
2-yl)-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide;
[0397] (236) 4-methyl-pentanoic
acid-{4-[1l-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino]-butyl}-amide; [0398] (237)
2-methoxy-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-benzamide; [0399] (238)
1-isopropyl-3-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tri-
azolo[4,3-a]quinoxaline-4-ylamino]-butyl}-urea; [0400] (239)
1-cyclohexyl-3-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-urea; [0401] (240)
3-methyl-N-{4-[1-methyl-7-(1-propyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0402] (241)
N-(4-{7-[1-(2-methoxy-ethyl)-1H-benzoimidazole-2-yl]-1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino}-butyl)-3-methyl-butyramide;
[0403] (242)
[4-(1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; [0404] (243)
[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; [0405] (244)
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide; [0406] (245)
N-[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide; [0407] (246)
[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester;
[0408] (247)
N-[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide; [0409] (248)
N-[4-(7-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-benzamide; [0410] (249)
[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; [0411] (250)
N-[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; [0412] (251)
N-[4-(7-acetylamino-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-benzamide; [0413] (252)
3-methyl-N-[4-(1-methyl-7-methylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; [0414] (253)
3-methyl-N-[4-(1-methyl-7-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; [0415] (254)
N-{4-[7-(3-cyano-propylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-3-methyl-butyramide; [0416] (255)
N-{4-[7-(3-isopropyl-ureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino]-butyl}-3-methyl-butyramide; [0417] (256)
N-{4-[7-(3-isopropyl-thioureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-3-methyl-butyramide; [0418] (257)
N-[4-(7-methanesulfonylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; [0419] (258)
3-methyl-N-{4-[1-methyl-7-(2,2,2-trifluoro-ethanesulfonylamino)-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0420] (259)
3-methyl-N-{4-[1-methyl-7-(propane-2-sulfonylamino)-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-butyramide; [0421] (260)
[4-(7-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; [0422] (261)
{4-[7-(4-chloro-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-tert-butylester; [0423] (262)
{4-[7-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester; [0424] (263)
[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; [0425] (264)
N.sup.1-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid; [0426] (265)
2,2-dimethyl-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide; [0427] (266)
3,3-dimethyl-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide; [0428] (267)
N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; [0429] (268)
2-chloro-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-benzamide; [0430] (269)
[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; [0431] (270)
N.sup.1-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid; [0432] (271)
2,2-dimethyl-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide; [0433] (272)
3,3-dimethyl-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide; [0434] (273)
N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; [0435] (274)
2-chloro-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-benzamide; [0436] (275)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; [0437] (276)
N.sup.1-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid; [0438] (277)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide; [0439] (278)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid isopropylester; [0440] (279)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid isobutylester; [0441] (280)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-sec-butylester; [0442] (281)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-isobutyramide; [0443] (282) cyclopropanecarboxylic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; [0444] (283) butene-2-oic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; [0445] (284) 3-methyl-butene-2-oic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; [0446] (285)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-butyramide; [0447] (286)
2-(S)-fluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; [0448] (287)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3,3-dimethyl-butyramide; [0449] (288) 4-methyl-pentanoic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; [0450] (289) 3-methyl-pentanoic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-amide; [0451] (290)
2-ethyl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-butyramide; [0452] (291)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-methyl-butyramide; [0453] (292)
2,2,3,3,4,4,4-heptafluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-4-ylamino)-butyl]-butyramide; [0454] (293)
3,3,3-trifluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-2,2-dimethyl-propaneamide; [0455] (294)
2,2-difluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; [0456] (295)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-propaneamide; [0457] (296) acetic
acid-1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butylcarbamoyl]-1-methyl-ethylester; [0458] (297)
2-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-2-methyl-propionamide; [0459] (298)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0460] (299)
2-(S)-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0461] (300)
2-(R)-methoxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0462] (301)
2-(S)-methoxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0463] (302)
2-(S)-bromo-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-3-methyl-butyramide; [0464] (303) acetic
acid-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butylcarbamoyl]-methylester; [0465] (304)
2-hydroxy-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-acetamide; [0466] (305)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-malonamic acid [0467] ethylester; [0468] (306)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-malonamic acid; [0469] (307)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-thiophene-2-yl-acetamide; [0470] (308)
2-furan-2-yl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-acetamide; [0471] (309)
3-cyclopentyl-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-propionamide; [0472] (310)
{-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
ylcarbamoyl]-2-methyl-propyl}-carbamic acid-tert-butylester; [0473]
(311)
2-amino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0474] (312)
2-(R)-dimethylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl]-3-methyl-butyramide; [0475] (313)
2-(S)-dimethylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl]-3-methyl-butyramide; [0476] (314)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-2-(S)-morpholine-4-yl-butyramide; [0477] (315)
2-(S)-(3-hydroxy-pyrrolidine-1-yl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0478]
(316)
2-(S)-(4-hydroxy-piperidine-1-yl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0479]
(317)
2-(S)-[4-(2-hydroxy-ethyl)-piperidine-1-yl]-N-[4-(7-methoxy-1-methyl-[1,2-
,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide;
[0480] (318)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid isobutylester;
[0481] (319)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid propylester;
[0482] (320)
(S)-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butylcarbamoyl]-2-methyl-propyl}-carbamic acid
isopropylester; [0483] (321)
(S)-2-(S)-fluoro-N-{1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino)-butyl
carbamoyl]-2-methyl-propyl}-3-methyl-butyramide; [0484] (322)
(S)--N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-3-methyl-2-(3-methyl-butyrylamino)-butyramide; [0485]
(323)
(S)-2-(2,2-dimethyl-propionylamino)-N-[4-(7-methoxy-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0486]
(324) 2-(S)-(2
(S)-hydroxy-propionylamino)-N-[4-(7-methoxy-1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide;
[0487] (325)
{2-(S)-(4-hydroxy-phenyl)-1-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-4-ylamino)-butylcarbamoyl]-ethyl}-carbamic
acid-tert-butylester; [0488] (326)
2-(S)-amino-3-(4-hydroxy-phenyl)-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino)-butyl]-propionamide; [0489] (327)
2-(S)-methanesulfonylamino-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0490] (328)
2-fluoro-N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-benzamide; [0491] (329)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2-phenyl-acetamide; [0492] (330)
1-isopropyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-urea; [0493] (331)
1-tert-butyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-urea; [0494] (332)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid cyclopentylester; [0495] (333)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid phenylester; [0496] (334)
3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-1,1-dimethyl-urea; [0497] (335)
1-cyclohexyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-urea; [0498] (336)
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-thiocarbamic acid-S-isopropylester; [0499] (337)
1-isopropyl-3-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-thiourea; [0500] (338)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-methanesulfonamide; [0501] (339)
N-{4-[7-methoxy-1-methyl-8-(4-nitro-benzyl)-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-3-methyl-butyramide; [0502] (340)
N-[4-(7-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-butyramide; [0503] (341)
N-{4-[7-(4-cyano-benzyloxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-3-methyl-butyramide; [0504] (342)
N-{4-[7-(3-cyano-propoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-3-methyl-butyramide; [0505] (343)
3-methyl-N-{4-[1-methyl-7-(tetrahydro-pyran-2-ylmethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide; [0506] (344)
3-methyl-N-{4-[1-methyl-7-(tetrahydro-pyran-4-yloxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-butyramide; [0507] (345)
4-{1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3-a]-
quinoxaline-7-yloxy}-piperidine-1-carboxylic acid-tert-butylester;
[0508] (346)
N-[4-(7-benzyloxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0509] (347)
N-(4-{7-[4-(N-hydroxycarbaimidolyl)-benzoyl]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino}-butyl)-3-methyl-butyramide; [0510] (348)
3-methyl-N-(4-{l-methyl-7-[4-(2H-tetrazol-5-yl)-benzyloxy]-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino}-butyl)-butyramide; [0511] (349)
3-methyl-N-(4-{1l-methyl-7-[4-(2-methyl-2H-tetrazolo-5-yl)-benzyloxy]-[1,-
2,4]triazolo[4,3-a]quinoxaline-4-ylamino}-butyl)-butyramide; [0512]
(350) benzoic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triaz-
olo[4,3-a]quinoxaline-7-yl-ester; [0513] (351)
morpholine-4-carboxylic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3--
a]quinoxaline-7-yl-ester; [0514] (352)
3-methyl-thiophene-2-carboxylic
acid-1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3--
a]quinoxaline-7-yl-ester; [0515] (353) dimethyl-thiocarbamic
acid-O-{1l-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[-
4,3-a]quinoxaline-7-yl}-ester; [0516] (354)
[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; [0517] (355)
N.sup.1-(1-methyl-(7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
l)-butane-1,4-diamine ditrifluoroacetic acid; [0518] (356)
3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; [0519] (357)
2-(S)-fluoro-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino)-butyl]-butyramide; [0520] (358)
2-(S)-hydroxy-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino)-butyl]-butyramide; [0521] (359)
N-[4-(7-methanesulfinyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0522] (360)
N-[4-(7-methanesulfonyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0523] (361)
[4-(7-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0524] (362)
4-(7-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-carbami-
c acid-tert-butylester; [0525] (363)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-tert-butylester; [0526] (364)
N.sup.1-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0527] (365)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-3-methyl-butyramide; [0528] (366)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid isopropylester;
[0529] (367)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid propylester; [0530] (368)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-sec-butylester; [0531] (369)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid isobutylester; [0532] (370)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid allylester; [0533] (371)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid cyclopentylester; [0534] (372)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid phenylester; [0535] (373)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid benzylester; [0536] (374)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-acetamide; [0537] (375)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-2,2-dimethyl-propionamide; [0538] (376)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-isobutyramide; [0539] (377) cyclopropanecarboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0540] (378) 3-methyl-butene-2-oic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0541] (379) butene-2-oic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0542] (380)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-methyl-butyramide; [0543] (381)
2-ethyl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-butyramide; [0544] (382)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-3,3-dimethyl-butyramide; [0545] (383)
4-methyl-pentanoic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0546] (384) acetic
acid-1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-1-methyl-ethylester; [0547] (385)
2-hydroxy-N-{4-(7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino)-butyl}-2-methyl-propionamide; [0548] (386) acetic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butylcarbamoyl}-methylester; [0549] (387)
2-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-acetamide; [0550] (388)
2-(R)-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0551] (389)
2-(S)-hydroxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0552] (390)
2-(R)-methoxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0553] (391)
2,2-difluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-butyramide; [0554] (392)
3,3,3-trifluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-2,2-dimethyl-propionamide; [0555]
(393)
3-cyclopentyl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-propionamide; [0556] (394)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-malonamic acid ethylester; [0557] (395)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-malonamic acid; [0558] (396)
(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid-tert-butylester; [0559] (397)
2-amino-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-3-methyl-butyramide; [0560] (398)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
isobutylester; [0561] (399)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
propylester; [0562] (400)
(S)-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic acid
isopropylester; [0563] (401)
(S)--N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-3-methyl-2-(3-methyl-butyrylamino)-butyramide;
[0564] (402)
(S)-2-(2,2-dimethyl-propionylamino)-N-{4-[7-(2-methoxy-ethoxy)-1-me-
thyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyrami-
de; [0565] (403)
2-(S,R)-hydroxy-N-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-3-methyl-butyr-
amide; [0566] (404)
2-(S,S)-hydroxy-N-(1-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-3-methyl-butyr-
amide; [0567] (405)
2-(S)-methanesulfonylamino-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0568]
(406)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-thiophene-2-yl-acetamide; [0569] (407)
2-furan-2-yl-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-acetamide; [0570] (408)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-benzamide; [0571] (409)
2-fluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; [0572] (410)
3-fluoro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; [0573] (411)
2-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; [0574] (412)
2-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-benzamide; [0575] (413)
2,3-dichloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-benzamide; [0576] (414)
2-methoxy-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-benzamide; [0577] (415)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-4-nitro-butyramide; [0578] (416)
pyridine-2-carboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0579] (417)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-nicotinamide; [0580] (418)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-isonicotinamide; [0581] (419)
6-chloro-N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-nicotinamide; [0582] (420)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-2-phenyl-acetamide; [0583] (421)
3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-1,1-dimethyl-urea; [0584] (422)
1-isopropyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-urea; [0585] (423)
1-ethyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-urea; [0586] (424)
1-tert-butyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-urea; [0587] (425)
morpholine-4-carboxylic
acid-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-amide; [0588] (426)
1-cyclohexyl-3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-urea; [0589] (427)
3-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-1-phenyl-urea; [0590] (428)
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-thiocarbamic acid-S-isopropylester; [0591] (429)
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-methanesulfonamide; [0592] (430)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0593] (431)
N.sup.1-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-yl]-butane-1,4-diamine trifluoroacetic acid; [0594]
(432)
3-methyl-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-butyramide; [0595] (433)
2,2-dimethyl-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino]-butyl}-propionamide; [0596] (434)
2-(R)-hydroxy-N-{4-[7-(2-morpholine-4-yl-ethoxy)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0597]
(435)
2-(S)-hydroxy-N-{4-[7-(2-morpholine-4-yl-ethoxy)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0598]
(436)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid isopropylester; [0599] (437)
{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-carbamic acid cyclopentylester; [0600] (438)
N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-2-thiophene-2-yl-acetamide; [0601] (439)
2-chloro-N-{4-[1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-benzamide; [0602] (440)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0603] (441)
N.sup.1-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine dihydrochloride; [0604] (442)
N-[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-3-methyl-butyramide; [0605] (443)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isopropylester; [0606] (444)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isobutylester; [0607] (445)
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid cyclopentylester; [0608] (446)
N-[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-2-thiophene-2-yl-acetamide; [0609] (447)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; [0610] (448)
N.sup.1-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; [0611] (449)
N-[-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide; [0612] (450)
N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-methyl-butyramide; [0613] (451)
N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-thiophene-2-yl-acetamide; [0614] (452)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; [0615] (453)
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid cyclopentylester; [0616] (454)
2-chloro-N-[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-benzamide; [0617] (455)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0618] (456)
N.sup.1-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; [0619] (457)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0620] (458)
[4-(7-methoxy-1,9-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide; [0621] (459)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; [0622] (460)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine dihydrochloride; [0623] (461)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; [0624] (462)
[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid isobutylester; [0625] (463)
N-[4-(6-chloro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-2-thiophene-2-yl-acetamide; [0626] (464)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0627] (465)
N.sup.1-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; [0628] (466)
N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide; [0629] (467)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0630] (468)
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; [0631] (469)
N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0632] (470)
2-chloro-N-[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-yl)-butyl]-benzamide; [0633] (471)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid-tert-butylester; [0634] (472)
N.sup.1-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; [0635]
(473)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isopropylester; [0636] (474)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid isobutylester; [0637] (475)
[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-carbamic acid cyclopentylester; [0638] (476)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-3-methyl-butyramide; [0639] (477)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-2,2-dimethyl-propionamide; [0640] (478)
2-(R)-hydroxy-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0641]
(479)
2-(S)-hydroxy-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0642]
(480)
N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino)-butyl]-2-thiophene-2-yl-acetamide; [0643] (481)
2-chloro-N-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino)-butyl]-benzamide; [0644] (482)
1-cyclohexyl-3-[4-(7-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4-
,3-a]quinoxaline-4-ylamino)-butyl]-urea; [0645] (483)
{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester;
[0646] (484)
N-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0647] (485)
N-{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; [0648] (486)
[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; [0649] (487)
N.sup.1-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; [0650] (488)
3-methyl-N-[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide; [0651] (489) 3-methyl-pentanoic
acid-[4-(6,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; [0652] (490)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; [0653] (491)
N.sup.1-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine dihydrochloride; [0654] (492)
N-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; [0655] (493)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isobutylester; [0656] (494)
[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isopropylester; [0657] (495)
3-methyl-pentanoic
acid-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide; [0658] (496)
N-[4-(7-imidazole-1-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-2-thiophene-2-yl-acetamide; [0659] (497)
[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; [0660] (498)
N.sup.1-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
l)-butane-1,4-diamine dihydrochloride; [0661] (499)
3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-butyramide; [0662] (500)
2-(S)-fluoro-3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino)-butyl]-butyramide; [0663] (501)
3-methyl-pentanoic
acid-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-amide; [0664] (502)
(S)-{2-methyl-1-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butylcarbamoyl]-propyl}-carbamic
acid-tert-butylester; [0665] (503)
2-(S)-amino-3-methyl-N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino)-butyl]-butyramide hydrochloride; [0666]
(504)
(S)-2-(2-(S)-hydroxy-propionylamino)-3-methyl-N-[4-(1-methyl-7-morpholine-
-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-butyramide
hydrochloride; [0667] (505)
2-(S)-methanesulfonylamino-3-methyl-N-[4-(1-methyl-7-morphonyl-4-yl-[1,2,-
4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-butyramide; [0668]
(506)
[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid isopropylester; [0669] (507)
N-[4-(1-methyl-7-morpholine-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-2-thiophene-2-yl-acetamide; [0670] (508)
{4-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0671] (509)
N.sup.1-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0672]
(510)
N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0673] (511)
N-{4-[7-(2,6-dimethyl-morphonyl-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino]-butyl}-2-(S)-fluoro-3-methyl-butyramide; [0674]
(512)
N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide;
[0675] (513)
(S)-(2-methyl-1-{4-[1-methyl-7-(2,6-dimethyl-morpholine-4-yl)-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-propyl)-carbamic
acid-tert-butylester; [0676] (514)
2-(S)-amino-N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide
hydrochloride; [0677] (515)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid isobutylester; [0678] (516)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid propylester; [0679] (517)
(S)--N.sup.1-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-2-(S)-f-
luoro-3-methyl-butyramide; [0680] (518)
(S)--N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-3-methyl-2-(3-methyl-butyrylamino)-butyram-
ide; [0681] (519)
(S)--N-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butyl}-2-(2,2-dimethyl-propionylamino)-3-methyl-b-
utyramide; [0682] (520)
(S)-(1-{4-[7-(2,6-dimethyl-morpholine-4-yl)-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino]-butylcarbamoyl}-2-methyl-propyl)-carbamic
acid isopropylester; [0683] (521)
{[4-(1-methyl-7-thiomorpholine-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-carbamic acid-tert-butylester; [0684] (522)
N.sup.1-(1-methyl-7-thiomorphonyl-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl)-butane-1,4-diamine ditrifluoroacetic acid; [0685] (523)
3-methyl-N-[4-(1-methyl-7-thiomorpholine-4-yl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino)-butyl]-butyramide; [0686] (524)
N-[4-(7-thiomorphonyl-4-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-2-(R)-hydroxy-3-methyl-butyramide; [0687] (525)
N-[4-(7-thiomorphonyl-4-yl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino)-butyl]-2-(S)-hydroxy-3-methyl-butyramide; [0688] (526)
{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino]-butyl}-carbamic
acid-tert-butylester; [0689] (527)
N.sup.1-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic
acid; [0690] (528)
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0691]
(529)
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-2-(S)-fluoro-3-methyl-butyramide;
[0692] (530)
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-carboxylic acid methylester; [0693] (531)
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-carboxylic acid; [0694] (532)
[4-(8-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester; [0695] (533)
[4-(8-carbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; [0696] (534)
4-(4-isobutyramido-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-8-carboxylic acid isopropylamide; [0697] (535)
4-(4-benzylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-
-carboxylic acid isopropylamide; [0698] (536)
{4-[8-(2-dimethylamino-ethylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0699]
(537)
4-(4-benzoylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-carboxyli-
c acid-(2-dimethylamino-ethyl)-amide; [0700] (538)
[4-(1-methyl-8-phenylcarbamoyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-carbamic acid-tert-butylester; [0701] (539)
N-{4-[8-(4-benzyl-piperazine-1-carbonyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-benzamide; [0702] (540)
N-{4-[1-methyl-8-(piperazine-1-carbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino]-butyl}-benzamide; [0703] (541)
[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; [0704] (542)
[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester; [0705] (543)
[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester; [0706] (544)
N-[4-(4-aminobutylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-yl]-
-isobutyramide ditrifluoroacetic acid; [0707] (545)
N-[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide; [0708] (546)
[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid-tert-butylester; [0709] (547)
N-[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide; [0710] (548)
N-[4-(8-acetamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-benzamide; [0711] (549)
N-[4-(8-isobutyramido-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-benzamide; [0712] (550)
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide; [0713] (551)
N-[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide; [0714] (552)
3-methyl-N-[4-(1-methyl-8-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-butyramide; [0715] (553)
N-{4-[8-(3-cyano-propylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino]-butyl}-3-methyl-butyramide; [0716] (554)
N-{4-[8-(3-ethyl-thioureido)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino]-butyl}-3-methyl-butyramide; [0717] (555)
N-[4-(7-methoxy-1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0718] (556)
N-[4-(8-amino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide; [0719] (557)
N-[4-(7-methoxy-1-methyl-8-methylamino-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0720] (558)
N-[4-(8-hydroxyamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-3-methyl-butyramide; [0721] (559)
N-[4-(7-methoxy-1-methyl-8-propylamino-[1,2,4]triazolo[4,3-a]quinoxaline--
4-ylamino)-butyl]-3-methyl-butyramide; [0722] (560)
N-[4-(7-methoxy-1-methyl-8-prop-2-ylamino-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-3-methyl-butyramide; [0723] (561)
N-{4-[8-(3-isopropyl-ureido)-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0724] (562)
N-{4-[7-methoxy-1-methyl-8-(3-methyl-butyrylamino)-[1,2,4]triazolo[4,3-a]-
quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0725] (563)
N-{7-methoxy-1-methyl-4-[4-(3-methyl-butyrylamino)-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-ylamino]-butyl}-3,3-dimethyl-butyramide; [0726] (564)
N-{4-[7-methoxy-1-methyl-8-(3-phenyl-ureido)-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-3-methyl-butyramide; [0727] (565)
N-[4-(8-methanesulfonylamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0728] (566)
N-[4-(8-dimethanesulfonylamino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino)-butyl]-3-methyl-butyramide; [0729] (567)
N-{4-[7-methoxy-1-methyl-8-(2-methyl-propane-1-sulfonylamino)-[1,2,4]tria-
zolo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide;
[0730] (568)
N-{4-[7-methoxy-1-methyl-8-(3-phenyl-ureido)-[1,2,4]triazolo[4,3-a]quinox-
aline-4-ylamino]-butyl}-3-methyl-butyramide; [0731] (569)
N-{4-[8-(3-isopropyl-thioureido)-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0732] (570)
{4-[8-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester; [0733] (571)
[4-(8-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester; [0734] (572)
[4-(8-fluoro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; [0735] (573)
[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester; [0736] (574)
N-[4-(8-fluoro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; [0737] (575)
N-[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; [0738] (576)
N-{4-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0739] (577)
N-{4-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide; [0740] (578)
{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0741] (579)
N.sup.1-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0742]
(580)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; [0743] (581)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; [0744]
(582)
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; [0745]
(583)
{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester; [0746] (584)
N.sup.1-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid; [0747]
(585)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide; [0748] (586)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(R)-hydroxy-3-methyl-butyramide; [0749]
(587)
N-{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-2-(S)-hydroxy-3-methyl-butyramide; [0750]
(588)
N.sup.1-[7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl]-butane-1,4-diamine ditrifluoroacetic acid; [0751] (589)
[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid isopropylester; [0752] (590)
N-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide; [0753] (591) 3-methyl-pentanoic
acid-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-amide; [0754] (592)
N.sup.1-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-yl)-butane-1,4-diamine ditrifluoroacetic acid; [0755] (593)
N-[4-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide; [0756] (594)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; [0757] (595)
N.sup.1-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; [0758] (596)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester;
[0759] (597)
N-[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide; [0760] (598)
[4-(1-ethyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; [0761] (599)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester; [0762] (600)
N.sup.1-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid; [0763] (601)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isopropylester; [0764] (602)
[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid isobutylester; [0765] (603)
N-[4-(1-isopropyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-3-methyl-butyramide; [0766] (604)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester; [0767] (605)
N.sup.1-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid; [0768] (606)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isopropylester; [0769] (607)
[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid isobutylester; [0770] (608)
N-[4-(1-phenyl-7,8-dimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-3-methyl-butyramide; [0771] (609)
[4-([1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; [0772] (610)
[4-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0773] (611)
N.sup.1-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine; [0774] (612)
N-[4-(1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-acetamide; [0775] (613)
[4-(1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; [0776] (614)
N.sup.1-(1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diami-
ne; [0777] (615)
[4-(1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carba-
mic acid-tert-butylester; [0778] (616)
N.sup.1-(1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-d-
iamine; [0779] (617)
[4-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester; [0780] (618)
N.sup.1-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diam-
ine; [0781] (619)
N-[4-(1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-acetam-
ide; [0782] (620)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester; [0783] (621)
N.sup.1-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine ditrifluoroacetic acid; [0784] (622)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-3-methyl-butyramide; [0785] (623)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isopropylester; [0786] (624)
[4-(7-methoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid isobutylester; [0787] (625)
[4-(7-methoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester; [0788] (626)
N.sup.1-(7-methoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid; [0789] (627)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-3-methyl-butyramide; [0790] (628)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isopropylester; [0791] (629)
[4-(1-isopropyl-7-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid isobutylester; [0792] (630)
4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butan-1-ol;
[0793] (631) 2,2-dimethyl-propionic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
[0794] (632) isobutyric
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-este-
r; [0795] (633) 3,3-dimethyl-butyric
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-este-
r; [0796] (634) benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
[0797] (635) 4-chloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
[0798] (636) 2,3-dichloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
[0799] (637) 2-chloro-benzoic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester;
[0800] (638)
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-ca-
rbamic acid-tert-butylester; [0801] (639)
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butylami-
ne ditrifluoroacetic acid; [0802] (640)
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-
]-3-methyl-butyramide; [0803] (641)
tert-butyl(2-((1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)amino)pent-
yl)carbamate; [0804] (642)
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid-tert-butylester; [0805] (643)
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-p-
entane-1,5-diamine ditrifluoroacetic acid; [0806] (644)
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid isopropylester; [0807] (645)
N-[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-pentyl]-2,2-dimethyl-propionamide; [0808] (646)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-tert-butylamide; [0809] (647)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid isopropylamide; [0810] (648)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid isobutylamide; [0811] (649)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(2-methyl-butyl)-amide; [0812] (650)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(furan-2-yl-methyl)-amide; [0813] (651)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid benzylamide; [0814] (652)
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-(1H-pyrrole-2-yl-methyl)-amide; [0815] (653)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-tert-butylamide; [0816] (654)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid isopropylamide; [0817] (655)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid isobutylamide; [0818] (656)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-(2-methyl-butyl)-amide; [0819] (657)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-(furan-2-yl-methyl)-amide; [0820] (658)
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-benzamide; [0821] (659)
5-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentanoic
acid isopropylamide; [0822] (660)
5-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentanoic
acid isobutylamide; [0823] (661)
6-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-hexanoic
acid isopropylamide; and [0824] (662)
6-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-hexanoic
acid isobutylamide.
[0825] The compound represented by formula 1 of the present
invention can be used as a form of a pharmaceutically acceptable
salt, in which the salt is preferably acid addition salt formed by
pharmaceutically acceptable free acids. The acid addition salt
herein can be obtained from inorganic acids such as hydrochloric
acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic
acid, hydroiodic acid, nitrous acid, and phosphorous acid;
non-toxic organic acids such as aliphatic mono/dicarboxylate,
phenyl-substituted alkanoate, hydroxy alkanoate, alkandioate,
aromatic acids, and aliphatic/aromatic sulfonic acids; or organic
acids such as acetic acid, benzoic acid, citric acid, lactic acid,
maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic
acid, tartaric acid, and fumaric acid. The pharmaceutically
non-toxic salts are exemplified by sulfate, pyrosulfate, bisulfate,
sulphite, bisulphite, nitrate, phosphate, monohydrogen phosphate,
dihydrogen phosphate, metaphosphate, pyrophosphate, chloride,
bromide, iodide, fluoride, acetate, propionate, decanoate,
caprylate, acrylate, formate, isobutylate, caprate, heptanoate,
propiolate, oxalate, malonate, succinate, suberate, cabacate,
fumarate, maliate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate,
chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate,
methoxybenzoate, phthalate, terephthalate, benzenesulfonate,
toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate,
phenylacetate, phenylpropionate, phenylbutylate, citrate, lactate,
hydroxybutylate, glycolate, malate, tartrate, methanesulfonate,
propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate,
and mandelate.
[0826] The acid addition salt in this invention can be prepared by
the conventional method known to those in the art. For example, the
derivative represented by formula 1 is dissolved in an organic
solvent such as methanol, ethanol, acetone, dichloromethane, and
acetonitrile, to which organic acid or inorganic acid is added to
induce precipitation. Then, the precipitate is filtered and dried
to give the salt. Or the solvent and the excessive acid are
distillated under reduced pressure, and dried to give the salt. Or
the precipitate is crystallized in an organic solvent to give the
same.
[0827] A pharmaceutically acceptable metal salt can be prepared by
using a base. Alkali metal or alkali earth metal salt is obtained
by the following processes: dissolving the compound in excessive
alkali metal hydroxide or alkali earth metal hydroxide solution;
filtering non-soluble compound salt; evaporating the remaining
solution and drying thereof. At this time, the metal salt is
preferably prepared in the pharmaceutically suitable form of
sodium, potassium, or calcium salt. And the corresponding silver
salt is prepared by the reaction of alkali metal or alkali earth
metal salt with proper silver salt (ex; silver nitrate).
[0828] The present invention includes not only the compound
represented by formula 1 but also a pharmaceutically acceptable
salt thereof, and a solvate, an optical isomer, or a hydrate
possibly produced from the same.
[0829] In another aspect of the present invention, the present
invention also provides a preparation method of the compound
represented by formula 1 comprising the following steps, as shown
in reaction formula 1 below:
[0830] preparing the compound represented by formula 4 by reacting
the compound represented by formula 2 with the compound represented
by formula 3 (step 1); and
[0831] preparing the compound represented by formula 1 by reacting
the compound represented by formula 4 prepared in step 1 above with
the compound represented by formula 5 (step 2):
##STR00033##
[0832] (In reaction formula 1,
[0833] R.sup.1.about.R.sup.6, M and X are independently as defined
in formula 1 above)
[0834] Hereinafter, the preparation method of the compound
represented by formula 1 of the present invention is described in
more detail, step by step.
[0835] In the preparation method of the compound represented by
formula 1 of the present invention, step 1 is to prepare the
compound represented by formula 4 by reacting the compound
represented by formula 2 with the compound represented by formula
3.
[0836] In the step above, the reaction temperature is not
particularly limited, but the reaction can be performed at
60.about.160.degree. C., preferably at 80.about.140.degree. C.,
more preferably at 90.about.120.degree. C., and most preferably at
100.degree. C.
[0837] In addition, the reaction time is not particularly limited,
but the reaction can be performed for 0.2.about.4 hours, preferably
for 0.5.about.3 hours, more preferably for 0.8.about.2 hours, and
most preferably for 1 hour.
[0838] In the preparation method of the compound represented by
formula 1 according to the present invention, step 2 is to prepare
the compound represented by formula 1 by reacting the compound
represented by formula 4 prepared in step 1 above with the compound
represented by formula 5.
[0839] In the step above, the reaction temperature is not
particularly limited, but the reaction can be performed at
10.about.100.degree. C., preferably at 50.about.100.degree. C.,
more preferably at 60.about.90.degree. C., and most preferably at
80.degree. C.
[0840] In addition, the reaction time is not particularly limited,
but the reaction can be performed for 1.about.24 hours, preferably
for 12.about.24 hours, more preferably for 16.about.20 hours, and
most preferably for 18 hours.
[0841] In another aspect of the present invention, the present
invention also provides a preparation method of the compound
represented by formula 1 comprising the following steps, as shown
in reaction formula 2 below:
[0842] preparing the compound represented by formula 8 by reacting
the compound represented by formula 7 with the compound represented
by formula 5 (step 1);
[0843] preparing the compound represented by formula 9 by reacting
the compound represented by formula 8 prepared in step 1 above with
hydrazine hydrate (step 2); and
[0844] preparing the compound represented by formula 1 by reacting
the compound represented by formula 9 prepared in step 2 above with
the compound represented by formula 3 (step 3):
##STR00034##
[0845] (In reaction formula 2,
[0846] R.sup.1.about.R.sup.6, M and X are independently as defined
in formula 1 above).
[0847] Hereinafter, the preparation method of the compound
represented by formula 1 of the present invention is described in
more detail, step by step.
[0848] In the preparation method of the compound represented by
formula 1 of the present invention, step 1 is to prepare the
compound represented by formula 8 by reacting the compound
represented by formula 7 with the compound represented by formula
5.
[0849] In the step above, the reaction temperature is not
particularly limited, but the reaction can be performed at
10.about.100.degree. C., preferably at 20.about.100.degree. C.,
more preferably at 20.about.90.degree. C., and most preferably at
80.degree. C.
[0850] In addition, the reaction time is not particularly limited,
but the reaction can be performed for 1.about.24 hours, preferably
for 12.about.24 hours, more preferably for 16.about.20 hours, and
most preferably for 18 hours.
[0851] In the preparation method of the compound represented by
formula 1 according to the present invention, step 2 is to prepare
the compound represented by formula 9 by reacting the compound
represented by formula 8 prepared in step 1 above with hydrazine
hydrate.
[0852] As an example, the compound represented by formula 8
prepared in the step 1 and hydrazine hydrate were dissolved in
ethanol, refluxed and stirred. Upon completion of the reaction, the
solvent was distilled under reduced pressure. Moisture was
eliminated over magnesium sulfate, followed by distillation and
drying under reduced pressure. As a result, the compound
represented by formula 9 was obtained.
[0853] In the step above, the reaction temperature is not
particularly limited, but the reaction can be performed at
10.about.80.degree. C., preferably at 25.about.80.degree. C., more
preferably at 40.about.80.degree. C., and most preferably at
80.degree. C.
[0854] In addition, the reaction time is not particularly limited,
but the reaction can be performed for 1.about.6 hours, preferably
for 1.5.about.5 hours, more preferably for 2.about.4 hours, and
most preferably for 3 hours.
[0855] In the preparation method of the compound represented by
formula 1 according to the present invention, step 3 is to prepare
the compound represented by formula 1 by reacting the compound
represented by formula 9 prepared in step 2 above with the compound
represented by formula 3.
[0856] In the step above, the reaction temperature is not
particularly limited, but the reaction can be performed at
60.about.160.degree. C., preferably at 80.about.140.degree. C.,
more preferably at 90.about.120.degree. C., and most preferably at
100.degree. C.
[0857] In addition, the reaction time is not particularly limited,
but the reaction can be performed for 0.2.about.4 hours, preferably
for 0.5.about.3 hours, more preferably for 0.8.about.2 hours, and
most preferably for 1 hour.
[0858] In an aspect of the present invention, the present invention
provides a pharmaceutical composition comprising the compound
represented by formula 1, the optical isomer thereof or the
pharmaceutically acceptable salt thereof as an active ingredient
for the prevention or treatment of BET (bromodomain extra-terminal)
protein related diseases.
[0859] Herein, the BET (bromodomain extra-terminal) protein related
disease above is characterized by cancer, which is preferably
exemplified by thymus cancer, blood cancer, ovarian cancer,
cervical cancer, breast cancer, colorectal cancer, liver cancer,
stomach cancer, pancreatic cancer, colon cancer, peritoneal
metastatic cancer, bladder cancer, prostate cancer, thyroid cancer,
lung cancer, osteosarcoma, fibroid tumor and brain tumor.
[0860] In addition, the BET (bromodomain extra-terminal) protein
related disease above is characterized by autoimmune disease, which
is preferably exemplified by rheumatoid arthritis, systemic lupus
erythematosus, multiple sclerosis, type 1 diabetes,
hyperthyroidism, myasthenia, Crohn's disease, ankylosing
spondylitis, psoriasis, autoimmune malignant anemia and Sjogren's
syndrome.
[0861] The formulations for oral administration are exemplified by
tablets, pills, hard/soft capsules, solutions, suspensions,
emulsions, syrups, granules, and elixirs, etc. These formulations
can include diluents (for example, lactose, dextrose, sucrose,
mannitol, sorbitol, cellulose, and/or glycine) and lubricants (for
example, silica, talc, stearate and its magnesium or calcium salt,
and/or polyethylene glycol) in addition to the active ingredient.
Tablets can include binding agents such as magnesium aluminum
silicate, starch paste, gelatin, methylcellulose, sodium
carboxymethylcellulose and/or polyvinylpyrolidone, and if necessary
disintegrating agents such as starch, agarose, alginic acid or its
sodium salt or azeotropic mixtures and/or absorbents, coloring
agents, flavours, and sweeteners can be additionally included
thereto.
[0862] The pharmaceutical composition comprising the compound
represented by formula 1 as an active ingredient can be
administered parenterally and the parenteral administration
includes subcutaneous injection, intravenous injection,
intramuscular injection and intrathoracic injection.
[0863] To prepare the composition as a formulation for parenteral
administration, the compound represented by formula 1 or the
pharmaceutically acceptable salt thereof are mixed with a
stabilizer or a buffering agent to produce a solution or
suspension, which is then formulated as ampoules or vials. The
composition herein can be sterilized and additionally contains
preservatives, stabilizers, wettable powders or emulsifiers, salts
and/or buffers for the regulation of osmotic pressure, and other
therapeutically useful materials, and the composition can be
formulated by the conventional mixing, granulating or coating
method.
[0864] The effective dosage of the compound represented by formula
1 of the present invention can vary depending on the patient's age,
weight, gender, administration form, health condition and disease
severity. Based on an adult patient weighing 70 kg, the dosage is
generally 0.1.about.1000 mg/day, and preferably 1.about.500 mg/day.
The compound of the present invention can be administered once or
several times a day at a predetermined time interval according to
the judgment of a doctor or a pharmacist.
[0865] The novel [1,2,4]triazolo[4,3-a]quinoxaline derivative
according to the present invention can inhibit the binding of BRD4,
one of BET protein family, at a low concentration, and displays
excellent cytotoxicity in tumor cells, so that it can be used as a
pharmaceutical composition for the prevention or treatment of BET
protein related diseases including cancer and autoimmune disease,
which is supported by the following experimental results.
[0866] In an aspect of the present invention, the present invention
provides a method for preventing, ameliorating or treating BET
(bromodomain extra-terminal) protein related diseases which
comprises a step of administering the pharmaceutical composition
comprising the compound represented by formula 1, the optical
isomer thereof or the pharmaceutically acceptable salt thereof as
an active ingredient to a subject.
[0867] In addition, in another aspect of the present invention, the
present invention provides a use of the pharmaceutical composition
comprising the compound represented by formula 1, the optical
isomer thereof or the pharmaceutically acceptable salt thereof as
an active ingredient.
[0868] Practical and presently preferred embodiments of the present
invention are illustrative as shown in the following Examples and
Experimental Examples.
[0869] However, it will be appreciated that those skilled in the
art, on consideration of this disclosure, may make modifications
and improvements within the spirit and scope of the present
invention.
<Preparative Example 1> Preparation of
4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00035##
[0870] Step 1: Preparation of 2-chloro-3-hydrazinylquinoxaline
[0871] Hydrazine hydrate (2.77 g, 55.3 mmol) was added dropwise to
ethanol containing 2,3-dichloroquinoxaline (5.00 g, 25.1 mmol) at
room temperature, followed by stirring at 25.degree. C. for 16
hours. The resulting precipitate was collected by filtration,
washed with ethanol and dried. As a result, a target compound
2-chloro-3-hydrazinylquinoxaline was obtained (95% yield) as pale
yellow powder.
[0872] Mass (M+H.sup.+): 195.0
Step 2: Preparation of
4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[0873] 2-Chloro-3 hydrazinylquinoxaline (5.00 g, 25.7 mmol)
obtained in step 1 of Preparative Example 1 was refluxed in
triethylorthoacetate solvent at 100.degree. C. for 1 hour. The
reaction mixture was cooled down at room temperature and the
resulting precipitate was filtered, washed with normal hexane and
dried under reduced pressure. As a result, a target compound was
obtained (91% yield) as a light grey solid.
[0874] Mass (M+H.sup.+): 219.0
[0875] .sup.1H NMR (300 MHz, DMSO-d6): .delta.3.11 (s, 3H), 7.72
(t, J=7.41 Hz, 1H), 7.81 (t, J=7.56 Hz, 1H), 8.03 (d, J=7.74 Hz,
1H), 8.37 (d, J=8.28 Hz, 1H).
<Example 1> Preparation of
[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00036##
[0877] Tert-butyl(4-aminobutyl)carbamate (2.50 g, 13.7 mmol) and
N,N-diisopropylethylamine (DIPEA, 4.79 ml, 27. mmol) were dissolved
in isopropyl alcohol.
4-Chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (2.00 g, 9.15
mmol) obtained in step 2 of Preparative Example 1 was added thereto
at room temperature. The reaction mixture was stirred at 40.degree.
C. for 1.5 hours. The reaction mixture was cooled down at room
temperature and the resulting white precipitate was collected by
filtration, washed with isopropyl alcohol and dried. As a result, a
target compound was obtained (89% yield).
[0878] Mass (M+H.sup.+): 371.2
[0879] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.45-1.51 (m, 2H), 1.63-1.68 (m, 2H), 2.93-3.02 (m, 2H), 3.02 (s,
3H), 3.50-3.57 (m, 2H), 7.29 (t, J=7.35 Hz, 1H), 7.44 (t, J=7.68
Hz, 1H), 7.60 (d, J=7.89 Hz, 1H), 8.07-8.11 (m, 2H).
<Example 2> Preparation of
N.sup.1-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,4-diam-
ine dihydrochloride
##STR00037##
[0881]
[4-(1-Methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-ca-
rbamic acid-tert-butylester obtained in Example 1 was dissolved in
ethylacetate, to which excessive amount of 4 M HCl and dioxane were
added. The reaction mixture was stirred at room temperature for 4
hours. The reaction mixture was concentrated to give a target
compound in the status of hydrochloride (quantitative yield), which
was used in the next step without any further purification
process.
[0882] Mass (M+H.sup.+): 271.2
[0883] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.62-1.68 (m, 2H),
1.73-1.77 (m, 2H), 2.83-2.90 (m, 2H), 3.05 (s, 3H), 3.58-3.61 (m,
2H), 7.33-7.36 (m, 1H), 7.47-7.50 (m, 1H), 7.64 (dd, J=8.15, 1.00
Hz, 1H), 7.72 (brs, 2H), 8.13 (d, J=8.1 Hz, 2H), 8.37 (brs,
1H).
<Example 3> Preparation of
2,2-dimethyl-N-[4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-propionamide
##STR00038##
[0885]
N.sup.1-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-1,-
4-diamine dihydrochloride obtained in Example 2 and DIPEA (4 eq.)
were dissolved in acetonitrile, to which trimethylacetylchloride
(1.10-1.50 eq.) was slowly added at 0.degree. C. The reaction
mixture was warmed to room temperature, followed by stirring at
room temperature for 1 hour. The reaction mixture was concentrated,
diluted in sodium bicarbonate solution and extracted with
ethylacetate three times. The organic layer was washed with brine,
dried over magnesium sulfate, concentrated and purified using MPLC
(isopropylalcohol/dimethylchloride). As a result, a target compound
was obtained (63% yield).
[0886] Mass (M+H.sup.+): 355.2
[0887] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.06 (s, 9H),
1.46-1.54 (m, 2H), 1.60-1.68 (m, 2H), 3.02 (s, 3H), 3.05-3.11 (m,
2H), 3.51-3.57 (m, 2H), 7.27-7.32 (m, 1H), 7.39-7.46 (m, 2H), 7.59
(dd, 1H), 8.07-8.12 (m, 2H).
[0888] The compounds shown in Table 1 below were prepared by the
same manner as described in Example 3.
TABLE-US-00001 TABLE 1 Example Structure Name Data Example 4
##STR00039## [4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline-
4- ylamino)- butyl]- carbamic Mass (M + H.sup.+): 356.1; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.14 (d, J = 6.25 Hz, 6H), 1.46-1.52
(m, 2H), 1.63-1.69 (m, 2H), 3.00-3.03 (m, 2H), 3.04 (s, 3H), 3.53-
3.57 (m, 2H), 4.70- 4.75 (m, 1H), 7.00 acid (t, J = 5.15 Hz,
isopropylester 1H), 7.31 (t, J = 7.35 Hz, 1H), 7.45 (t, J = 7.65
Hz, 1H) , 7.62 (d, J = 7.85 Hz, 1H), 8.10- 8.14 (m, 2H). Example 5
##STR00040## [4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline-
4- ylamino)- butyl]- acetamide Mass (M + H.sup.+): 313.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.44- 1.53 (m, 2H), 1.63- 1.73 (m,
2H), 1.78 (s, 3H), 3.03 (s, 3H), 3.04-3.11 (m, 2H), 3.54-3.61 (m,
2H), 7.34 (t, J = 7.26 Hz, 1H), 7.48 (t, J = 7.53 Hz, 1H), 7.65 (d,
J = 7.95 Hz, 1H), 7.82 (t, J = 4.29 Hz, 1H), 8.11 (d, J = 8.19 Hz,
1H), 8.52 (brs, 1H). Example 6 ##STR00041## [4-(1- methyl- [1,2,4]
triazolo [4,3-a] quinoxaline- 4- ylamino)- butyl]- isobutyramide
Mass (M + H.sup.+): 341.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.97 (d, J = 6.85 Hz, 6H), 1.46-1.52 (m, 2H), 1.64-1.70 (m,
2H), 2.29-2.34 (m, 1H), 3.04 (s, 3H), 3.06- 3.10 (m, 2H), 3.53-
3.57 (m, 2H), 7.29- 7.33 (m, 1H), 7.45 (t, J = 7.20 Hz, 1H), 7.60
(dd, J = 7.90 Hz, 0.80 Hz, 1H), 7.70 (t, J = 5.05 Hz, 1H), 8.10 (d,
J = 8.15 Hz, 1H), 8.14 (t, J = 5.60 Hz, 1H). Example 7 ##STR00042##
3-methyl-N- [4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-
ylamino)- butyl]- Mass (M + H.sup.+): 355.2; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.0.83 (d, J = 6.15 Hz, 6H), 1.46-1.52 (m, 2H),
1.65-1.71 (m, 2H), 1.91-1.97 (m, 3H), 3.04 (s, 3H), 3.07- 3.11 (m,
2H), 3.53- 3.57 (m, 2H), 7.31 butyramide (t, J = 7.50 Hz, 1H), 7.45
(t, J = 7.65 Hz, 1H), 7.61 (d, J = 7.95 Hz, 1H), 7.75 (t, J = 5.25
Hz, 1H), 8.10 (d, J = 8.30 Hz, 1H), 8.14 (t, J = 5.70 Hz, 1H).
Example 8 ##STR00043## 3,3- dimethyl- N-[4-(1- methyl- [1,2,4]
triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- Mass (M +
H.sup.+): 369.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.0.92 (s,
9H),1.43-1.53 (m, 2H), 1.63-1.72 (m, 2H), 1.92 (s, 2H), 3.03-3.11
(m, 5H), 3.51-3.58 (m, 2H), 7.27-7.33 (m, 1H), 7.44 (t, J = 7.38
butyramide Hz, 1H), 7.59-7.62 (m, 1H), 7.69 (t, J = 5.28 Hz, 1H),
8.08-8.14 (m, 2H). Example 9 ##STR00044## 2-(R)- hydroxy-N- [4-(1-
methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3-
methyl- Mass (M + H.sup.+): 371.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.68 (d, 3H), 0.83 (d, 3H), 1.49 (m, 2H), 1.62 (m, 2H), 1.90
(m, 1H), 2.98 (s, 3H), 3.13 (m, 2H), 3.51 (q, 2H), 3.59 (d, 1H),
5.23 (d, 1H), 7.26 (q, 1H), 7.39 butyramide (q, 1H), 7.54 (d, 1H),
7.65 (t, 1H), 8.03 (d, 1H), 8.08 (t, 1H). Example 10 ##STR00045##
2-(S)- hydroxy-N- [4-(1- methyl- [1,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+): 371.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H),
1.49 (m, 2H), 1.62 (m, 2H), 1.90 (m, 1H), 2.98 (s, 3H), 3.13 (m,
2H), 3.51 (q, 2H), 3.59 (d, 1H), 5.23 (d, 1H), methyl- 7.26 (q,
1H), 7.39 butyramide (q, 1H), 7.54 (d, 1H), 7.65 (t, 1H), 8.03 (d,
1H), 8.08 (t, 1H). Example 11 ##STR00046## N-[4-(1- methyl-
[1,2,4]tria zolo[4,3- a]quinoxali ne-4- ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 374.5; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.63- 1.66 (m, 2H), 1.75- 1.78 (m, 2H), 3.04 (s, 3H),
3.31-3.35 (m, 2H), 3.62-3.64 (m, 2H), 7.36-7.39 (m, 1H), 7.44 (t, J
= 7.20 Hz, 2H), 7.48-7.52 (m, 1H), 7.68 (d, J = 7.95 Hz, 1H),
7.82-7.83 (m, 2H), 8.12 (d, J = 8.10 Hz, 1H), 8.48 (t, J = 5.50 Hz,
1H), 8.83 (brs, 1H). Example 12 ##STR00047## 2-chloro-N- [4-(1-
methyl- [1,2,4[tria zolo[4,3- a]quinoxali ne-4- ylamino)- butyl]-
benzamide Mass (M + H.sup.+): 409.2; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.1.57- 1.66 (m, 2H), 1.72- 1.82 (m, 2H), 3.03 (s,
3H), 3.25-3.31 (m, 2H), 3.56-3.62 (m, 2H), 7.28-7.52 (m, 7H), 7.61
(dd, J = 8.07, 1.14 Hz, 1H), 8.09-8.16 (m, 2H), 8.40 (t, J = 5.46
Hz,1H). Example 13 ##STR00048## 2,6- dimethyl-N- [4-(1- methyl-
[1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- Mass (M +
H.sup.+): 403.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.58- 1.66
(m, 2H), 1.71- 1.78 (m, 2H), 2.17 (s, 6H), 3.03 (s, 3H), 3.25-3.31
(m, 2H), 3.55-3.61 (m, 2H), 6.99 (d, J = 7.56 Hz, 2H), 7.13
benzamide (t, J = 7.65 Hz, 1H), 7.31 (t, J = 7.23 Hz, 1H), 7.45 (t,
J = 7.41 Hz, 1H), 7.60 (d, J = 7.95 Hz, 1H), 8.10 (d, J = 8.22 Hz,
1H), 8.15 (t, J = 5.67 Hz, 1H), 8.25 (t, J = 5.19 Hz, 1H). Example
14 ##STR00049## 4-chloro-N- [4-(1- methyl- [1,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- benzamide Mass (M + H.sup.+):
409.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.59- 1.76 (m, 4H),
3.02 (s, 3H), 3.28-3.34 (m, 2H), 3.55-3.61 (m, 2H), 7.27-7.32 (m,
1H), 7.43 (t, J = 7.41 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.57 (d,
J = 7.95 Hz, 1H), 7.83 (d, J = 8.49 Hz, 2H), 8.07-8.13 (m, 2H),
8.51 (t, J = 5.37 Hz, 1H). Example 15 ##STR00050## 3-chloro-N-
[4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)-
butyl]- benzamide Mass (M + H.sup.+): 409.2; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.1.60- 1.76 (m, 4H), 3.02 (s, 3H), 3.28-3.35 (m,
2H), 3.55-3.61 (m, 2H), 7.26-7.32 (m, 1H), 7.40-7.49 (m, 2H), 7.58
(d, J = 7.95 Hz, 2H), 7.85 (brs, 1H), 8.07-8.13 (m, 2H), 8.58 (t, J
= 5.28 Hz, 1H). Example 16 ##STR00051## 3,4- dichloro-N- [4-(1-
methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-
Mass (M + H.sup.+): 443.1; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.60- 1.77 (m, 4H), 3.03 (s, 3H), 3.31-3.35 (m, 2H),
3.55-3.61 (m, 2H), 7.27-7.33 (m, 1H), 7.40-7.45 (m, 1H), 7.55-7.58
benzamide (m, 1H), 7.71 (d, J = 8.97 Hz, 1H), 7.79 (dd, J = 8.40
Hz, 1.65 Hz, 1H), 7.04 (d, J = 1.86 Hz, 1H), 8.08-8.14 (m, 2H),
8.63 (t, J = 5.37 Hz, 1H). Example 17 ##STR00052## 2,3- dichloro-N-
[4-(1-] methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)-
butyl]- Mass (M + H.sup.+): 443.1; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.58- 1.65 (m, 2H), 1.72- 1.77 (m, 2H), 3.03 (s, 3H),
3.25-3.32 (m, 2H), 3.55-3.62 (m, 2H), 7.28-7.39 (m, 3H), 7.45 (t, J
= 7.80 Hz, 1H), benzamide 7.60 (d, J = 7.92 Hz, 1H), 7.67 (dd, J =
6.63 Hz, 2.79 Hz, 1H), 8.10 (d, J = 8.22 Hz, 1H), 8.16 (t, J = 5.52
Hz, 1H), 8.51 (t, J = 5.43 Hz, 1H). Example 18 ##STR00053## 3,5-
dichloro-N- [4-(1- methyl- [1,2,4]tria zolo[4,3- a]quinoxali ne-4-
ylamino)- butyl]- Mass (M + H.sup.+): 443.1; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.1.58- 1.79 (m, 4H), 3.03 (s, 3H), 3.29-3.33 (m,
2H), 3.55-3.61 (m, 2H), 7.27-7.32 (m, 1H), 7.43 (t, J= 7.68 Hz,
1H), 7.57 (d, J =7.95 benzamide Hz, 1H), 7.77 (d, J = 1.56 Hz, 1H),
7.85 (d, J = 1.68 Hz, 2H), 8.08-8.16 (m, 2H), 8.75 (t, J = 5.19 Hz,
1H). Example 19 ##STR00054## 2,6- dichloro-N- [4-(1- methyl-
[1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- Mass (M +
H.sup.+): 444.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.58 (m,
2H), 1.72 (m, 2H), 3.99 (s, 3H), 3.24 (m, 2H), 3.54 (q, 2H), 7.27
(t, 1H), 7.41 (t, 1H), 7.57 (d, 2H), 7.89 (s, 1H), 8.06 (d, 1H),
nicotinamide 8.12 (t, 1H), 8.57 (t, 1H). Example 20 ##STR00055##
6-chloro-N- [4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline-
4-ylamino)- butyl]- nicotinamide Mass (M + H.sup.+): 410.1; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.50 (m, 2H), 1.70 (m, 2H), 2.98 (s,
3H), 3.30 (q, 2H), 3.54 (q, 2H), 7.26 (t, 1H), 7.38 (t, 1H), 7.52
(d, 1H), 7.56 (d, 1H), 8.06 (d, 1H), 8.10 (t, 1H), 8.16 (d, 1H),
8.66 (t, 1H), 8.76 (s, 1H). Example 21 ##STR00056## 2-chloro-6-
methyl-N- [4-(1- methyl- [1,2,4] triazolo [4,3-a] quinoxaline-4-
ylamino)- butyl]- Mass (M + H.sup.+): 424.2; .sup.1NMR (500 MHz,
DMSO-d6): .delta.1.57 (m, 2H), 1.72 (m, 2H), 2.42 (s, 3H), 7.24 (d,
1H), 7.27 (t, 1H), 7.42 (t, 1H), 7.56 (d, 1H), 7.68 (d, 1H), 8.06
(d, 1H), 8.11 (t, 1H), nicotinamide 8.44 (t, 1H). Example 22
##STR00057## 1-tert- butyl-3-[4- (1-methyl- [1,2,4] triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]-urea Mass (M + H.sup.+):
370.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.15 (s, 9H), 1.39
(m, 2H), 1.61 (m, 2H), 2.94 (q, 2H), 2.99 (s, 3H), 3.51 (q, 2H),
5.48 (s, 1H), 5.56 (t, 1H), 7.26 (t, 1H), 7.40 (t, 1H), 7.56 (d,
1H), 8.06 (d, 1H), 8.09 (m, 1H). Example 23 ##STR00058## 1-(4-
fluoro- phenyl)-3- [4-(1- methyl- [1,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]-urea Mass (M + H.sup.+): 476.1;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.1.47 (m, 2H), 1.65 (m, 2H),
7.98 (s, 3H), 3.08 (q, 2H), 3.51 (q, 2H), 6.05 (t, 1H), 6.98 (t,
2H), 7.31 (m, 2H), 7.73 (s, 1H), 8.10 (s, 1H), 8.35 (s, 1H), 8.49
(t, 1H). Example 24 ##STR00059## 1-(3- fluoro- phenyl)-3- [4-(1-
methyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)-
butyl]-urea Mass (M + H.sup.+): 408.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.49 (m, 2H), 1.66 (m, 2H), 2.98 (s, 3H), 3.09 (q,
2H), 3.53 (q, 2H), 6.17 (t, 1H), 6.63 (td, 1H), 6.95 (d, 1H), 7.18
(dd, 1H), 7.27 (t, 1H), 7.39 (m, 2H), 7.56 (d, 1H), 8.05 (dd, 1H),
8.11 (t, 1H), 8.58 (s, 1H). Example 25 ##STR00060## [4-(1- methyl-
[1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- carbamic
acid benzylester Mass (M + H.sup.+): 405.2; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.1.46- 1.56 (m, 2H), 1.64- 1.73 (m, 2H), 3.04 (s,
3H), 3.07-3.09 (m, 2H), 3.54-3.60 (m, 2H), 5.00 (s, 2H), 7.26-7.37
(m, 7H), 7.47 (t, J = 7.41 Hz, 1H), 7.65 (d, J = 8.34 Hz, 1H), 8.11
(d, J = 7.86 Hz, 1H), 8.55 (brs, 1H).
<Preparative Example 2> Preparation of
4,7,8-trichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00061##
[0889] Step 1: Preparation of
2,6,7-trichloro-3-hydrazinylquinoxaline
[0890] 9.23 g of a target compound was obtained (94% yield) by the
same manner as described in step 1 of Preparative Example 1, except
that 2,3,6,7-tetrachloroquinoxaline (10.0 g, 37.3 mmol) was
used.
[0891] Mass (M+H.sup.+): 264.0
Step 2: Preparation of
4,7,8-trichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[0892] 7.9 g of a target compound was obtained (79% yield) by the
same manner as described in step 2 of Preparative Example 1, except
that 2,6,7-trichloro-3-hydrazinylquinoxaline (9.2 g, 34.9 mmol)
prepared in step 1 of Preparative Example 2 was used.
[0893] Mass (M+H.sup.+): 288.1
[0894] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.09 (s, 3H), 7.20
(s, 1H), 8.35 (s, 1H), 7.41 (s, 1H).
<Example 26> Preparation of
[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester
##STR00062##
[0896] 4.5 g of a target compound was obtained (98% yield) by the
same manner as described in Example 1 except that
4,7,8-trichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline prepared
in step 2 of Preparative Example 2 was used as a starting
material.
[0897] Mass (M+H.sup.+): 439.1
[0898] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.41 (m,
2H), 1.59 (m, 2H), 2.91 (q, 2H), 3.27 (s, 3H), 3.49 (q, 2H), 6.74
(t, 1H), 7.74 (s, 1H), 8.11 (s, 1H), 8.46 (t, 1H)
<Example 27> Preparation of
N.sup.1-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)but-
ane-1,4-diamine ditrifluoroacetic acid
##STR00063##
[0900]
[4-(7,8-Dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester (4 g, 9.1 mmol) prepared
in Example 26 was dissolved in 100 ml of dichloromethane, to which
trifluoroacetic acid (17 ml, 228 mmol) was added, followed by
stirring at room temperature for 4 hours. The reaction mixture was
concentrated under reduced pressure, followed by recrystallization
in methanol and ether. The resulting compound was dried under
reduced pressure and as a result 3.2 g of a target compound was
obtained (78% yield) in the state of TFA salt.
[0901] Mass (M+H.sup.+): 339.1
[0902] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.58 (m, 2H), 1.68
(m, 2H), 2.18 (q, 2H), 3.00 (s, 3H), 3.52 (q, 2H), 7.60 (brm, 2H),
7.72 (s, 1H), 8.13 (s, 1H), 8.52 (t, 1H).
<Example 28> Preparation of
N-[4-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2,2-dimethyl-propionamide
##STR00064##
[0904] 190 mg of a target compound was obtained (82% yield) by the
same manner as described in Example 3, except that
N.sup.1-(7,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)but-
ane-1,4-diamine ditrifluoroacetic acid (250 mg, 0.55 mmol) prepared
in Example 27 was used.
[0905] Mass (M+H.sup.+): 423.1
[0906] .sup.1H NMR (250 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.44
(m, 2H) 1.60 (m, 2H), 2.98 (s, 3H), 3.05 (q, 2H), 3.49 (m, 2H),
7.36 (t, 1H), 7.72 (s, 1H), 8.11 (s, 1H).
[0907] The compounds shown in Table 2 below were prepared by the
same manner as described in Example 28.
TABLE-US-00002 TABLE 2 Example Structure Name Data Example 29
##STR00065## N-[4-(7,8- dichloro-1- methyl- [,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- isobutyramide Mass (M + H.sup.+):
409.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.93 (d, 6H), 1.42
(m, 2H), 1.61 (m, 2H), 2.37 (m, 1H), 2.98 (s, 3H), 3.03 (m, 2H),
3.49 (q, 2H), 7.62 (t, 1H), 7.73 (s, 1H), 8.11 (s, 1H), 8.48 (t,
1H). Example 30 ##STR00066## N-[4-(7,8- dichloro-1- methyl- [1,2,4]
triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M
+ H.sup.+): 424.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.86 (m, 2H), 1.88 (m, 1H), 2.99
(s, 3H), 3.48 (q, 2H), 3.50 (q, 2H), 3.80 butyramide (s, 3H), 7.70
(t, 1H), 7.73 (s, 1H), 8.11 (s, 1H), 8.48 (t, 1H). Example 31
##STR00067## N-[4-(7,8- dichloro-1- methyl- [1,2,4] triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]- benzamide Mass (M +
H.sup.+): 443.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.57 (m,
2H), 1.68 (m, 2H), 2.98 (s, 3H), 3.28 (m, 2H), 3.54 (q, 2H), 7.38
(m, 2H), 7.46 (t, 1H), 7.70 (s, 1H), 7.77 (d, 1H), 8.10 (s, 1H),
8.39 (t, 1H), 8.48 (t, 1H). Example 32 ##STR00068## 2-chloro-N-
[4-(7,8- dichloro-1- methyl- [1,2,4] triazolo[ [4,3-a] quinoxaline-
4-ylamino)- butyl]- Mass (M + H.sup.+): 477.1; .sup.1NMR (500 MHz,
DMSO-d6): .delta.1.56 (m, 1H), 1.71 (m, 2H), 2.99 (s, 3H), 3.24 (q,
2H), 3.54 (q, 2H), 7.27~7.40 (m, 3H), 7.42 (d, 1H), 7.73 (s, 1H),
benzamide 8.12 (s, 1H), 8.35 (t, 1H), 8.50 (t, 1H). Example 33
##STR00069## 6-chloro-N- [4-(7,8- dichloro-1- methyl- [1,2,4]
triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- Mass (M +
H.sup.+): 479.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m,
2H), 1.70 (m. 2H), 2.98 (s, 3H), 3.28 (q, 2H), 3.52 (q, 2H), 7.56
(d, 1H), 7.67 (s, 1H), 8.10 (s, 1H), 8.14 nicotinamide (m, 1H),
8.65 (t, 1H), 8.74 (t, 1H).
[0908] A 7,8-dimethyl[1,2,4]triazolo[4,3-a]quinoxaline compound can
be prepared using a
4-chloro-1,7,8-trimethyl-[1,2,4]triazolo[4,3-a]quinoxaline compound
by the same manner as described in Preparative Example 2.
<Example 34> Preparation of
[4-(1,7,8-trimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-c-
arbamic acid-tert-butylester
##STR00070##
[0910] Mass (M+H.sup.+): 399.2
[0911] .sup.1H NMR (300 MHz, CDCl.sub.3): .delta.1.44 (s, 9H),
1.64-1.66 (m, 2H), 1.76-1.80 (m, 2H), 2.36 (s, 3H), 2.39 (s, 3H),
3.09 (s, 3H), 3.21-3.24 (m, 2H), 3.69-3.71 (m, 2H), 4.74 (brs, 1H),
6.17 (brs, 1H), 7.55 (s, 1H), 7.70 (s, 1H).
[0912] A 7,8-difluoro[1,2,4]triazolo[4,3-a]quinoxaline compound can
be prepared using a
4-chloro-7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
compound by the same manner as described in Preparative Example
2.
<Example 35> Preparation of
[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester
##STR00071##
[0914] Mass (M+H.sup.+): 407.3
[0915] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.40-1.50 (m, 2H), 1.56-1.69 (m, 2H), 2.90-2.97 (m, 2H), 3.00 (s,
3H), 3.48-3.55 (m, 2H), 6.78 (brs, 1H), 7.56-7.62 (m, 1H),
8.05-8.11 (m, 1H), 8.32 (t, J=5.67 Hz, 1H).
<Example 36> Preparation of
N.sup.1-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid
##STR00072##
[0917]
[4-(7,8-Difluoro-1-methyl-1-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester (1.6 g, 3.96 mmol)
prepared in Example 35 was dissolved in 50 ml of dichloromethane,
to which trifluoroacetic acid (5.8 ml, 79 mmol) was added, followed
by stirring at room temperature for 4 hours. The reaction mixture
was concentrated under reduced pressure, followed by
recrystallization in methanol and ether. The resulting compound was
dried under reduced pressure and as a result 1.73 g of a target
compound was obtained (82% yield) in the state of TFA salt.
[0918] Mass (M+H.sup.+): 307.2
<Example 37> Preparation of
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-3-methyl-butyramide
##STR00073##
[0920]
N.sup.1-(7,8-Difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)butane-1,4-diamine ditrifluoroacetic acid (200 mg, 0.37 mmol)
prepared in Example 36 was dissolved in 5 ml of dichloromethane, to
which triethylamine (0.26 ml, 1.87 mmol, 5 eq) and
isovalerylchloride (1.15 ml, 0.44 mmol, 1.2 eq) were added at
0.about.10.degree. C. stepwise. The reaction mixture was stirred at
room temperature for 2 hours. Upon completion of the reaction, the
reaction was terminated by using methanol, followed by distillation
under reduced pressure. The reactant was separated and purified by
column chromatography, and as a result 140 mg of a target compound
was obtained (97% yield).
[0921] Mass (M+H.sup.+): 391.1
[0922] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.43
(m, 2H), 1.61 (m, 2H), 1.86 (d, 2H), 1.90 (m, 1H), 2.97 (s, 3H),
3.04 (q, 2H), 3.49 (q, 2H), 7.55 (dd, 1H), 7.69 (t, 1H), 8.06 (dd,
1H), 8.29 (t, 1H).
<Example 38> Preparation of
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(R)-hydroxy-3-methyl-butyramide
##STR00074##
[0924]
N.sup.1-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)butane-1,4-diamine ditrifluoroacetic acid (200 mg, 0.37 mmol)
prepared in Example 36 was dissolved in 5 ml of tetrahydrofuran, to
which diisopropylethylamine (DIPEA, 0.33 ml, 1.87 mmol, 5 eq),
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI, 140 mg, 2 eq),
hydroxybenzotriazol (HOBt, 100 mg, 2 eq), and
2-(R)-hydroxy-3-methyl-butyric acid (88 mg, 2 eq) were added
stepwise, followed by stirring at room temperature for 3 hours.
Upon completion of the reaction, the reactant was extracted with
dichloromethane and water. The organic layer was dried over
anhydrous magnesium sulfate, and distilled under reduced pressure.
The reactant was separated and purified by column chromatography,
and as a result 84 mg of a target compound was obtained (55%
yield).
[0925] Mass (M+H.sup.+): 407.2
[0926] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.72 (d, 3H), 0.85 (d,
3H), 1.51 (m, 2H), 1.65 (m, 2H), 1.92 (m, 1H), 2.98 (s, 3H), 3.15
(m, 2H), 3.53 (q, 2H), 3.61 (q, 1H), 5.01 (d, 1H), 7.45 (t, 1H),
7.53 (q, 1H), 8.03 (d, 1H), 8.05 (t, 1H).
<Example 39> Preparation of
N-[4-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)--
butyl]-2-(S)-hydroxy-3-methyl-butyramide
##STR00075##
[0928] 90 mg of a target compound was obtained (59% yield) by the
same manner as described in Example 38, except that
N.sup.1-(7,8-difluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)but-
ane-1,4-diamine ditrifluoroacetic acid (200 mg, 0.37 mmol) prepared
in Example 36 and 2-(S)-hydroxy-3-methyl-butyric acid (88 mg, 2 eq)
were used.
[0929] Mass (M+H.sup.+): 407.2
[0930] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.72 (d, 3H), 0.85 (d,
3H), 1.51 (m, 2H), 1.65 (m, 2H), 1.92 (m, 1H), 2.98 (s, 3H), 3.15
(m, 2H), 3.53 (q, 2H), 3.61 (q, 1H), 5.01 (d, 1H), 7.45 (t, 1H),
7.53 (q, 1H), 8.03 (d, 1H), 8.05 (t, 1H).
<Preparative Example 3> Preparation of
4-chloro-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00076##
[0931] Step 1: Preparation of
(3-chloro-7-methyl-quinoxaline-2-yl)-hydrazine
[0932] A target compound was obtained (57% yield) by the same
manner as described in step 1 of Preparative Example 1, except that
2,3-dichloro-6-methylquinoxaline (1 g, 4.69 mmol) was used.
[0933] Mass (M+H.sup.+): 209.1
Step 2: Preparation of
4-chloro-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
[0934] A target compound was obtained by the same manner as
described in step 2 of Preparative Example 1, except that
(3-chloro-7-methyl-quinoxaline-2-yl)-hydrazine (0.17 g, 0.82 mmol)
prepared in step 1 of Preparative Example 3 was used. The following
reaction was carried out without purification.
[0935] Mass (M+H.sup.+): 233.1
<Example 40> Preparation of
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carb-
amic acid-tert-butylester
##STR00077##
[0937] 0.22 g of a target compound was obtained (two steps, 71%
yield) by the same manner as described in Example 1, except that
4-chloro-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline prepared in
step 2 of Preparative Example 3 was used.
[0938] Mass (M+H.sup.+): 385.2
[0939] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.37 (s, 9H),
1.45-1.49 (m, 2H), 1.60-1.66 (m, 2H), 2.46 (s, 3H), 2.95-2.99 (m,
2H), 3.04 (s, 3H), 3.50-3.54 (m, 2H), 6.81 (t, J=5.30 Hz, 1H), 7.27
(d, J=8.20 Hz, 1H), 7.51 (d, J=8.20 Hz, 1H), 7.88 (s, 1H), 7.99 (t,
J=5.85 Hz, 1H).
<Example 41> Preparation of
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butane]-1,4-
-diamine dihydrochloride
##STR00078##
[0941] 0.60 g of a target compound was obtained (quantitative
yield) by the same manner as described in Example 2, except that
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carb-
amic acid-tert-butylester prepared in Example 40 was used.
[0942] Mass (M+H.sup.+): 285.2
<Example 42> Preparation of
N-[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-2,-
2-dimethyl-propionamide
##STR00079##
[0944] 0.11 g of a target compound was obtained (59% yield) by the
same manner as described in Example 3, except that
[4-(1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butane]-1,4-
-diamine dihydrochloride prepared in Example 41 was used.
[0945] Mass (M+H.sup.+): 368.1
[0946] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.06 (s, 9H),
1.45-1.54 (m, 2H), 1.61-1.70 (m, 2H), 2.46 (s, 3H), 3.05 (s, 3H),
3.08-3.12 (m, 2H), 3.51-3.57 (m, 2H), 7.29 (d, J=8.04 Hz, 1H), 7.43
(t, J=5.37 Hz, 1H), 7.53 (d, J=8.19 Hz, 1H), 7.89 (s, 1H), 8.37
(brs, 1H).
[0947] The compounds shown in Table 3 below were prepared by the
same manner as described in Example 42.
TABLE-US-00003 TABLE 3 Example Structure Name Data Example 43
##STR00080## N-[4-(1,8- dimethyl- [1,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- isobutyramide Mass (M + H.sup.+):
355.6; .sup.1H NMR (300 MHz, DMSO-d6): .delta.0.97 (d, J = 6.84 Hz,
6H), 1.43-1.53 (m, 2H), 1.61-1.71 (m, 2H), 2.27-2.36 (m, 1H), 3.00
(s, 3H), 2.44 (s, 3H), 3.02-3.10 (m, 2H), 3.49-3.56 (m, 2H), 7.26
(d, J = 9.09 Hz, 1H), 7.49 (d, J = 8.19 Hz, 1H), 7.68 (t, J = 5.28
Hz, 1H), 7.88 (s, 1H), 7.97(t, J = 5.67 Hz, 1H). Example 44
##STR00081## 1-tert-- butyl-3- [4-(1,8- dimethyl- [1,2,4] triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]- Mass (M + H.sup.+): 384.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.1.20 (s, 9H), 1.40-1.46 (m,
2H), 1.62-1.68 (m, 2H), 2.46 (s, 3H), 2.97-3.00 (m, 2H), 3.05 (s,
3H), 3.51-3.55 (m, 2H), urea 5.54 (s, 1H), 5.62 (t, J = 5.50 Hz,
1H), 7.27 (d, J = 8.20 Hz, 1H), 7.51(d, J = 8.20 Hz, 1H), 7.89 (s,
1H), 8.00 (t, J = 5.75 Hz, 1H). Example 45 ##STR00082## N-[4-(1,8-
dimethyl- [1,2,4] triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-
benzamide Mass (M +H.sup.+): 388.3; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.61- 1.66 (m, 2H), 1.71-1.75 (m, 2H), 2.45 (s, 3H), 3.04
(s, 3H), 3.55-3.59 (m, 2H), 7.26 (d, J = 8.20 Hz, 1H), 7.42-7.52
(m, 4H), 7.82 (d, J = 7.65 Hz, 2H), 7.87 (s, 1H), 8.00 (t, J = 5.60
Hz, 1H), 3.30-3.36 (m, 2H), 8.46 (t, J = 5.40 Hz, 1H). Example 46
##STR00083## 1-[4-(1,8- dimethyl- [1,2,4] triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]-3- phenyl- urea Mass (M +H.sup.+):
404.2; .sup.1 H NMR (300 MHz, DMSO-d6): .delta.1.50- 1.56 (m, 2H),
1.67-1.73 (m, 2H), 2.46 (s, 3H), 3.04 (s, 3H), 3.12-3.16 (m, 2H),
3.54-3.58 (m, 2H), 6.13 (t, J = 5.55 Hz, 1H), 6.87 (t, J = 7.30 Hz,
1H), 7.20 (t, J = 7.90 Hz, 2H), 7.27 (d, J = 8.15 Hz, 1H), 7.36 (d,
J = 7.95 Hz, 2H), 7.51 (d, J = 8.20 Hz, 1H), 7.89 (s, 1H), 8.02 (t,
J = 5.70 Hz, 1H), 8.37 (s, 1H).
<Preparative Example 4> Preparation of
4-chloro-8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00084##
[0949] 4-Chloro-8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
was prepared by the same manner as the preparation of
4-chloro-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline described
in Preparative Example 3.
Step 1: Preparation of
(3-chloro-7-fluoro-quinoxaline-2-yl)-hydrazine
[0950] Mass (M+H.sup.+): 209.1
Step 2: Preparation of
4-chloro-8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[0951] Mass (M+H.sup.+): 237.0
[0952] .sup.1H NMR (300 MHz, DMSO-d6): .delta.3.11 (s, 3H),
7.60-7.67 (m, 1H), 8.09-8.17 (m, 2H)
<Example 47> Preparation of
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester
##STR00085##
[0954] 0.38 g of a target compound was obtained (82% yield) by the
same manner as described in Example 1, except that
4-chloro-8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared in step 2 of Preparative Example 4 was used.
[0955] Mass (M+H.sup.+): 389.2
[0956] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.44-1.48 (m, 2H), 1.62-1.68 (m, 2H), 2.95-2.98 (m, 2H), 3.03 (s,
3H), 3.50-3.54 (m, 2H), 6.81 (t, J=5.30 Hz, 1H), 7.31-7.35 (m, 1H),
7.61-7.64 (m, 1H), 7.86-7.88 (m, 1H), 8.12 (t, J=5.60 Hz, 1H),
<Example 48> Preparation of
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-1,4-diamine dihydrochloride
##STR00086##
[0958] 0.36 g of a target compound was obtained (quantitative
yield) by the same manner as described in Example 2, except that
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester prepared in Example 47 was used.
[0959] Mass (M+H.sup.+): 289.1
<Example 49> Preparation of
N-[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-2,2-dimethyl-propionamide
##STR00087##
[0961] 0.10 g of a target compound was obtained (70% yield) by the
same manner as described in Example 3, except that
[4-(8-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-1,4-diamine dihydrochloride prepared in Example 48 was used.
[0962] Mass (M+H.sup.+): 372.3
[0963] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.07 (s, 9H),
1.46-1.52 (m, 2H), 1.62-1.68 (m, 2H), 3.03 (s, 3H), 3.06-3.10 (m,
2H), 3.51-3.55 (m, 2H), 7.32-7.36 (m, 1H), 7.43 (t, J=5.45 Hz, 1H),
7.60-7.63 (m, 1H), 7.87-7.89 (m, 1H), 8.13 (t, J=5.70 Hz, 1H).
[0964] The compounds shown in Table 4 below were prepared by the
same manner as described in Example 49.
TABLE-US-00004 TABLE 4 Example Structure Name Data Example 50
##STR00088## [4-(8-fluoro-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- isobutyramide Mass (M + H.sup.+):
359.2; .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta.0.97 (d, J =
6.84 Hz, 6H), 1.45-1.52 (m, 2H), 1.61-1.69 (m, 2H), 2.28-2.33 (m,
1H), 3.03-3.09 (m, 2H), 3.02 (s, 3H), 3.50-3.56 (m, 2H), 7.32-7.36
(m, 1H), 7.30-7.37 (m, 1H), 7.59-7.69 (m, 2H), 7.85-7.90 (m, 1H),
8.10 (t, J = 5.70 Hz, 1H). Example 51 ##STR00089## N-[4-(8-fluoro-
1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
benzamide Mass (M + H.sup.+): 392.4; .sup.1H NMR (300 MHz,
DMSO-d.sub.6): .delta.1.60-1.69 (m, 2H), 1.71-1.78 (m, 2H), 3.02
(s, 3H), 3.29-3.35 (m, 2H), 3.54-3.62 (m, 2H), 7.29-7.35 (m, 1H),
7.40-7.53 (m, 3H), 7.58-7.63 (m, 1H), 7.80-7.83 (m, 2H), 7.85-7.89
(m, 1H), 8.12 (t, J = 5.67 Hz, 1H), 8.44 (t, J = 5.37 Hz, 1H).
Example 52 ##STR00090## 1-tert-butyl-3- [4-(8-fluoro-
1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
urea Mass (M + H.sup.+): 388.1; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.20 (s, 9H), 1.40-1.46 (m, 2H), 1.62-1.68
(m, 2H), 2.97-3.01 (m, 2H), 3.03 (s, 3H), 3.51-3.56 (m, 2H), 5.54
(s, 1H), 5.62 (t, J = 5.55 Hz, 1H), 7.32-7.36 (m, 1H), 7.62-7.65
(m, 1H), 7.87-7.90 (m, 1H), 8.14 (t, J = 5.70 Hz, 1H). Example 53
##STR00091## 1-[4-(8-fluoro- 1-methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 3-phenyl-urea Mass (M + H.sup.+):
408.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.50-1.56 (m,
2H), 1.67-1.73 (m, 2H), 3.03 (s, 3H), 3.12-3.16 (m, 2H), 3.54-3.58
(m, 2H), 6.13 (t, J = 5.60 Hz, 1H), 6.87 (t, J = 7.30 Hz, 1H), 7.20
(t, J = 8.10 Hz, 2H), 7.30-7.34 (m, 1H), 7.36 (d, J = 7.75 Hz, 2H),
7.62-7.64 (m, 1H), 7.87-7.89 (m, 1H), 8.16 (t, J = 5.75 Hz, 1H),
8.37 (s, 1H).
<Example 54> Preparation of
[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester
##STR00092##
[0966] 1.05 g of a target compound was obtained (3 steps, 48%
yield) by the same manner as described in Example 1, except that
4,8-dichloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline was
used.
[0967] Mass (M+H.sup.+): 405.2
[0968] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.37 (s, 9H),
1.45-1.49 (m, 2H), 1.62-1.68 (m, 2H), 2.95-2.99 (m, 2H), 3.03 (s,
3H), 3.51-3.55 (m, 2H), 6.80 (t, J=5.45 Hz, 1H), 7.47 (dd, J=8.70
Hz, 2.20 Hz, 1H), 7.59 (d, J=8.70 Hz, 1H), 8.01 (d, J=2.20 Hz, 1H),
8.28 (t, J=5.70 Hz, 1H).
<Example 55> Preparation of
N.sup.1-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)butane--
1,4-diamine hydrochloride
##STR00093##
[0970] A target compound was obtained by the same manner as
described in Example 2, except that
[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester prepared in Example 54 was used.
[0971] Mass (M+H.sup.+): 342.2
<Example 56> Preparation of
N-[4-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-benzamide
##STR00094##
[0973] A target compound was obtained by the same manner as
described in Example 11, except that
N.sup.1-(8-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)butane--
1,4-diamine hydrochloride prepared in Example 55 was used.
[0974] Mass (M+H.sup.+): 408.2
[0975] NMR .sup.1H NMR (500 MHz, DMSO): .delta.1.50-1.56 (m, 2H),
1.67-1.73 (m, 2H), 3.03 (s, 3H), 3.12-3.16 (m, 2H), 3.54-3.58 (m,
2H), 6.13 (t, J=5.60 Hz, 1H), 6.87 (t, J=7.30 Hz, 1H), 7.20 (t,
J=8.10 Hz, 2H), 7.30-7.34 (m, 1H), 7.36 (d, J=7.75 Hz, 2H),
7.62-7.64 (m, 1H), 7.87-7.89 (m, 1H), 8.16 (t, J=5.75 Hz, 1H), 8.37
(s, 1H).
<Preparative Example 5> Preparation of
4-chloro-7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00095##
[0976] Step 1: Preparation of
2,3-dichloro-6,7-dimethoxy-quinoxaline
[0977] 6,7-Dimethoxy-1,4-dihydro-quinoxaline-2,3-dione (6.5 g, 29.3
mmol) and triethylamine (6.1 ml, 44.0 mmol) were reflux stirred in
70 ml of POCl.sub.3 for 18 hours. The reaction was slowly
terminated using methanol:water mixture (1:1) carefully not to
induce exothermic reaction. At this time, the resulting solid was
filtered and vacuum dried. As a result, 4.9 g of a target compound
was obtained (65% yield).
[0978] Mass (M+H.sup.+): 260.0
[0979] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.94 (s, 6H), 7.42
(s, 2H).
Step 2: Preparation of
(3-chloro-6,7-dimethoxy-quinoxaline-2-yl)-hydrazine
[0980] 2,3-Dichloro-6,7-dimethoxy-quinoxaline (4.9 g, 18.9 mmol)
prepared in step 1 of Preparative Example 5, triethylamine (26 ml,
189 mmol) and hydrazine hydrate (1.4 ml, 28.4 mmol) were dissolved
in 50 ml of ethanol, followed by stirring at 60-70.degree. C. for
21 hours. Upon completion of the reaction, the temperature was
lowered to room temperature and the resulting solid was filtered
and dried under reduced pressure. As a result, 4.4 g of a target
compound was obtained (91% yield).
[0981] Mass (M+H.sup.+): 255.1
[0982] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.81 (s, 3H), 3.86
(s, 3H), 4.40 (brs, 2H), 7.06 (s, 1H), 7.16 (s, 1H), 8.34 (s,
1H).
Step 3: Preparation of
4-chloro-7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[0983] (3-Chloro-6,7-dimethoxy-quinoxaline-2-yl)-hydrazine (4.39 g,
17.2 mmol) prepared in step 2 of Preparative Example 5 was reflux
stirred in 50 ml of triethylorthoacetate for 8 hours. Upon
completion of the reaction, the temperature was lowered to room
temperature, followed by recrystallization in methanol. The
resulting solid was filtered and dried under reduced pressure. As a
result, 3.7 g of a target compound was obtained (77% yield).
[0984] Mass (M+H.sup.+): 279.1
[0985] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.15 (s, 3H), 3.88
(s, 3H), 4.00 (s, 3H), 7.54 (s, 1H), 7.69 (s, 1H).
<Example 57> Preparation of
[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester
##STR00096##
[0987]
4-Chloro-7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
(2 g, 7.18 mmol) prepared in step 3 of Preparative Example 5,
diisopropylethylamine (DIPEA, 2.5 ml, 14.4 mmol) and
tert-butyl-N-(4-aminobutyl)carbamate (2.75 ml, 14.4 mmol) were
reflux stirred in 20 ml of isopropyl alcohol for 18 hours. Upon
completion of the reaction, the temperature was lowered to room
temperature, followed by recrystallization in methanol. The
resulting solid was filtered and dried under reduced pressure. As a
result, 2.86 g of a target compound was obtained (93% yield).
[0988] Mass (M+H.sup.+): 431.2
[0989] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43
(m, 2H), 1.59 (m, 2H), 2.92 (q, 2H), 3.03 (s, 3H), 3.47 (q, 2H),
3.82 (s, 3H), 3.86 (s, 3H), 6.75 (t, 1H), 7.09 (s, 1H), 7.50 (s,
1H), 7.81 (t, 1H).
<Example 58> Preparation of
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid
##STR00097##
[0991]
[4-(7,8-Dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-carbamic acid-tert-butylester (2.75 g, 5.97 mmol)
prepared in Example 57 was diluted in 30 ml of dichloromethane, to
which trifluoroacetic acid (9.14 ml, 119 mmol) was added, followed
by stirring at room temperature for 2 hours. Upon completion of the
reaction, the solvent was eliminated by distillation under reduced
pressure, followed by recrystallization in 10 ml of methanol. The
resulting solid was filtered and vacuum dried. As a result, 2.95 g
of a target compound was obtained (88% yield).
[0992] Mass (M+H.sup.+): 331.2
[0993] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.68
(m, 2H), 2.81 (q, 2H), 3.51 (q, 2H), 3.82 (s, 3H), 3.88 (s, 3H),
7.10 (s, 1H), 7.53 (s, 1H), 7.62 (brs, 3H), 7.98 (brs, 1H).
<Example 59> Preparation of
N-[4-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide
##STR00098##
[0995]
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-yl)-butane-1,4-diamine ditrifluoroacetic acid (250 mg, 0.45 mmol)
prepared in Example 58 and triethylamine (0.31 ml, 2.25 mmol) were
dissolved in 5 ml of dichloromethane. The temperature of the
mixture was lowered to 0-5.degree. C. and then
trimethylacetylchloride (0.07 ml, 0.54 mmol) was slowly added
thereto. The reaction mixture was stirred at the same temperature
as the above for 2 hours and then the reaction was terminated using
methanol. The reactant was distilled under reduced pressure,
followed by recrystallization in methanol. The resulting solid was
filtered and vacuum dried. As a result, 160 mg of a target compound
was obtained (86% yield).
[0996] Mass (M+H.sup.+): 415.2
[0997] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.46
(m, 2H), 1.60 (m, 2H), 3.03 (s, 3H), 3.05 (q, 2H), 3.47 (q, 2H),
3.82 (s, 3H), 3.87 (s, 3H), 7.09 (s, 1H), 7.37 (t, 1H), 7.51 (s,
1H), 7.81 (t, 1H).
[0998] The compounds shown in Table 5 below were prepared by the
same manner as described in Example 59.
TABLE-US-00005 TABLE 5 Example Structure Name Data Example 60
##STR00099## [4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- carbamic acid isopropylester Mass
(M + H.sup.+): 417.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6):
.delta.1.10 (d, 6H), 1.45 (m, 2H), 1.60 (m, 2H), 2.96 (q, 2H), 3.03
(s, 3H), 3.47 (q, 2H), 3.82 (s, 3H), 3.86 (s, 3H), 4.68 (m, 1H),
6.94 (t, 1H), 7.09 (s, 1H), 7.50 (s, 1H), 7.80 (t, 1H). Example 61
##STR00100## [4-(7,8- dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- carbamic acid ethylester Mass (M +
H.sup.+): 403.2; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.1.23 (t,
3H), 1.66 (m, 2H), 1.79 (m, 2H), 3.08 (s, 3H), 3.27 (q, 2H), 3.68
(q, 2H), 3.97 (d, 6H), 4.10 (q, 2H), 4.92 (s, 1H), 6.23 (t, 1H),
7.25 (t, 1H), 7.44 (s, 1H). Example 62 ##STR00101## [4-(7,8-
dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- carbamic acid isobutylester Mass (M + H.sup.+):
431.2; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.0.89 (d, 6H), 1.29
(brs, 1H), 1.66 (m, 2H), 1.77 (m, 2H), 1.78 (m, 2H), 1.85 (m, 1H),
3.10 (s, 3H), 3.26 (q, 2H), 3.63 (q, 2H), 3.82 (d, 2H), 3.97 (d,
6H), 4.88 (brs, 1H), 6.21 (brs, 1H), 7.45 (s, 1H). Example 63
##STR00102## [4-(7,8- dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- carbamic acid- sec-butylester Mass
(M + H.sup.+): 431.2; .sup.1H NMR (500 MHz, CDCl.sub.3):
.delta.0.79 (t, 3H), 1.07 (d, 3H), 1.42 (m, 4H), 1.60 (m, 2H), 2.97
(q, 2H), 3.03 (s, 3H), 3.47 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H),
4.53 (m, 1H), 6.96 (t, 1H), 7.10 (s, 1H), 7.52 (s, 1H), 7.82 (t,
1H). Example 64 ##STR00103## [4-(7,8- dimethoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- carbamic acid
propylester Mass (M + H.sup.+): 417.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.0.83 (t, 3H), 1.45 (m,2H), 1.49 (m, 2H), 1.50
(m, 2H), 2.97 (q, 2H), 3.04 (s, 3H), 3.50 (q, 2H), 3.82 (t, 2H),
3.83 (s, 3H), 3.87 (s, 3H), 7.02 (t, 1H), 7.10 (s, 1H), 7.52 (s,
1H), 7.81 (t, 1H). Example 65 ##STR00104## [4-(7,8- dimethoxy-
1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
carbamic acid allylester Mass (M + H.sup.+): 415.2; .sup.1H NMR
(500 MHz, CDCl.sub.3): .delta.0.87 (m, 1H), 1.68 (m, 1H), 1.79 (m,
2H), 3.10 (s, 1H), 3.29 (q, 2H), 3.70 (q, 2H), 4.10 (d, 6H), 4.55
(d, 2H), 5.01 (brs, 1H), 5.19 (d, 1H), 5.29 (d, 1H), 5.90 (m, 1H),
6.20 (brs, 1H), 7.46 (s, 1H) Example 66 ##STR00105## [4-(7,8-
dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- carbamic acid cyclopentyl- ester Mass (M +
H.sup.+): 443.2; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.1.55
(brs, 2H), 1.65 (m, 6H), 1.78 (m, 4H), 3.08 (s, 3H), 3.25 (q, 2H),
3.69 (q, 2H), 3.97 (d, 6H), 4.79 (brs, 1H), 5.07 (brs, 1H), 6.22
(brs, 1H), 7.22 (s, 1H), 7.44 (s, 1H). Example 67 ##STR00106##
[4-(7,8- dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- carbamic acid phenylester Mass (M + H.sup.+):
451.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.55 (m, 2H),
1.68 (m, 2H), 3.04 (s, 3H), 3.09 (q, 2H), 3.52 (q, 2H), 3.80 (s,
3H), 3.87 (s, 3H), 7.02 (d, 2H), 7.14 (m, 2H), 7.31 (m, 2H), 7.52
(s, 1H), 7.70 (t, 1H), 7.90 (brs, 1H). Example 68 ##STR00107##
[4-(7,8- dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- carbamic acid benzylester Mass (M + H.sup.+):
465.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.46 (m, 2H),
1.64 (m, 2H), 3.00 (q, 2H), 3.02 (s, 3H), 3.48 (q, 2H), 3.82 (s,
3H), 3.87 (s, 3H), 4.95 (s, 2H), 7.09 (s, 1H), 7.29 (m, 4H), 7.52
(s, 1H), 9.36 (t, 1H). Example 69 ##STR00108## N-[4-(7,8-
dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- acetamide Mass (M + H.sup.+): 373.2; .sup.1H NMR
(500 MHz, DMSO-d.sub.6): .delta.1.45 (m, 2H), 1.63 (m, 2H), 1.73
(s, 3H), 3.02 (q, 2H), 3.04 (s, 3H), 3.48 (q, 2H), 3.82 (s, 3H),
3.87 (s, 3H), 7.10 (s, 1H), 7.52 (s, 1H), 7.75 (t, 1H), 7.81 (t,
1H). Example 70 ##STR00109## N-[4-(7,8- dimethoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- isobutyramide Mass
(M + H.sup.+): 400.47; .sup.1H NMR (500 MHz, DMSO-d.sub.6):
.delta.0.93 (d, 6H), 1.45 (m, 2H), 1.61 (m, 2H), 2.27 (m, 1H), 3.02
(s, 3H), 3.03 (q, 2H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H),
7.09 (s, 1H), 7.51 (s, 1H), 7.63 (t, 1H), 7.81 (t, 1H). Example 71
##STR00110## 3-methyl-butene- 2-oic acid-[4- (7,8-dimethoxy-
1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
amide Mass (M + H.sup.+): 413.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.45 (m, 2H), 1.62 (m, 2H), 2.01 (s, 2H),
2.39 (s, 6H), 3.03 (q, 2H), 3.05 (s, 3H), 3.47 (q, 2H), 3.81 (s,
3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.52 (s, 1H), 7.65 (t, 1H), 7.81
(t, 1H). Example 72 ##STR00111## butene-2-oic acid-[4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-
4-ylamino)- butyl]-amide Mass (M + H.sup.+): 399.2, .sup.1H NMR
(500 MHz, DMSO-d.sub.6): .delta.1.44 (m, 2H), 1.62 (m, 2H), 2.46
(d, 3H), 2.82 (d, 1H), 3.04 (q, 2H), 3.05 (s, 3H), 3.48 (q, 2H),
3.82 (s, 3H), 3.87 (s, 3H), 5.04 (m, 1H), 7.10 (s, 1H), 7.52 (s,
1H), 7.77 (t, 1H), 7.81 (t, 1H). Example 73 ##STR00112## 3-methyl-
pentanoic acid- [4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- amide Mass (M +
H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.7 6
(m, 6H), 1.06 (m, 1H), 1.23 (m, 1H), 1.43 (m, 2H), 1.62 (m, 2H),
1.76 (m, 1H), 1.79 (m, 1H), 1.97 (m, H), 3.04 (q, 2H), 3.06 (s,
3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.52
(s, 1H), 7.08 (t, 1H), 7.81 (t, 1H). Example 74 ##STR00113##
N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 3-methyl- butyramide Mass (M +
H.sup.+): 415.3; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.0.93 (d,
6H), 1.58 (d, 2H), 1.66 (m, 2H), 1.80 (m, 2H), 2.09 (q, 2H), 2.10
(m, 1H), 3.11 (s, 3H), 3.36 (q, 2H), 3.71 (d, 1H), 3.99 (s, 6H),
5.50 (t, 1H), 6.15 (t, 1H), 7.47 (s, 1H). Example 75 ##STR00114##
N-[4-(7,8- dimethoxy- 1-methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 3,3-dimethyl- butyramide Mass (M +
H'): 429.3; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.88 (s,
9H), 1.44 (m, 2H), 1.62 (m, 2H), 1.88 (s, 2H), 3.02 (s, 3H), 3.05
(q, 2H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H), 7.09 (s, 1H),
7.51 (s, 1H), 7.64 (t, 1H), 7.81 (t, 1H). Example 76 ##STR00115##
cyclopropane- carboxylic acid-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- amide Mass (M +
H.sup.+): 399.0; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.55
(t, 2H), 0.60 (t, 2H), 1.45 (m, 1H), 1.46 (m, 2H), 1.65 (m, 2H),
3.03 (s, 3H), 3.06 (q, 2H), 3.49 (q, 3H), 3.82 (s, 3H), 3.87 (s,
3H), 7.10 (s, 1H), 7.52 (s, 1H), 7.81 (t, 1H), 7.97 (t, 1H).
Example 77 ##STR00116## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 2-methyl-
butyramide Mass (M + H.sup.+): 415.2; .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta.0.88 (t, 3H), 1.11 (d, 3H), 1.40 (m, 1H), 1.66
(m, 3H), 1.78 (m, 2H), 2.07 (m, 1H), 3.09 (s, 3H), 3.35 (q, 2H),
3.62 (brs, 2H), 3.97 (d, 2H), 5.64 (brs, 1H), 6.25 (brs, 1H), 7.25
(s, 1H), 7.44 (s, 1H). Example 78 ##STR00117## N-[4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- 2-ethyl- butyramide Mass (M + H.sup.+): 429.2;
.sup.1H NMR (500 MHz, CDCl.sub.3): .delta.0.88 (m, 6H), 1.45 (m,
2H), 1.79 (m, 2H), 3.08 (s, 3H), 3.36 (q, 2H), 3.69 (d, 2H), 3.97
(d, 6H), 5.65 (brs, 1H), 6.25 (brs, 1H), 7.22 (s, 1H), 7.52 (s,
1H). Example 79 ##STR00118## 4-methyl- pentanoic acid [4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- amide Mass (M + H.sup.+): 429.2; .sup.1H NMR (500
MHz, DMSO-d.sub.6): .delta.0.79 (d. 6H), 1.32 (m, 2H), 1.40 (m,
3H), 1.75 (m, 2H), 1.99 (m, 2H), 3.03 (q, 2H), 3.08 (s, 3H), 3.47
(q, 2H), 3.82 (s, 3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.52 (s, 1H),
7.71 (t, 1H), 7.82 (t, 1H). Example 80 ##STR00119## N-[4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- 2-methoxy- acetamide Mass (M + H.sup.+): 403.2;
.sup.1H NMR (500 MHz, CDCl.sub.3): .delta.1.69 (brs, 2H), 1.70 (m,
2H), 1.80 (m, 2H), 3.10 (s, 3H), 3.36 (q, 2H), 3.93 (s, 3H), 3.71
(brs, 1H), 3.88 (s, 2H), 3.99 (d, 6H), 6.60 (brs, 1H), 6.60 (brs,
1H), 7.47 (s, 1H). Example 81 ##STR00120## 3-cyclopentyl-
N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- propionamide Mass (M + H1): 455.3;
.sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.03 (m, 2H), 1.42 (m,
2H), 1.45 (m, 8H), 1.63 (m, 2H), 2.01 (m, 2H), 2.20 (m, 1H), 3.03
(q, 2H), 3.05 (s, 3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H),
7.10 (s, 1H), 7.51 (s, 1H), 7.69 (t, 1H), 7.81 (t, 1H). Example 82
##STR00121## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 2-(R)-hydroxy- 3-methyl- butyramide
Mass (M + H.sup.+): 431.2; NMR (500 MHz, DMSO-d.sub.6): .delta.0.69
(d, 3H), 0.82 (d, 3H), 1.23 (m, 1H), 1.48 (m, 2H), 1.61 (m, 2H),
1.90 (m, 1H), 3.03 (s, 3H), 3.13 (q, 2H), 3.48 (q, 2H), 3.60 (s,
1H), 3.82 (s, 3H), 3.90 (s, 3H), 5.23 (brs, 1H), 7.10 (s, 1H), 7.51
(s, 1H), 7.65 (t, 1H), 7.83 (t, 1H). Example 83 ##STR00122##
N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 2-(S)-hydroxy- 3-methyl- butyramide
Mass (M + H.sup.+): 431.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6):
.delta.0.69 (d, 3H), 0.82 (d, 3H), 1.23 (m, 1H), 1.48 (m, 2H), 1.61
(m, 2H), 1.90 (m, 1H), 3.03 (s, 3H), 3.13 (q, 2H), 3.48 (q, 2H),
3.60 (s, 1H), 3.82 (s, 3H), 3.90 (s, 3H), 5.23 (brs, 1H), 7.10 (s,
1H), 7.51 (s, 1H), 7.65 (t, 1H), 7.83 (t, 1H). Example 84
##STR00123## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 2-thiophene- 2-yl-acetamide Mass (M
+ H.sup.+): 455.2; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.1.61
(m, 2H), 1.80 (m, 2H), 3.10 (s, 3H), 3.30 (m, 2H), 3.70 (brs, 2H),
3.77 (s, 2H), 4.01 (d, 6H), 5.76 (brs, 1H), 6.20 (brs, 2H), 6.95
(s, 1H), 6.95 (d, 1H), 7.20 (d, 1H), 7.47 (s, 1H), 7.69 (t, 1H),
7.81 (t, 1H). Example 85 ##STR00124## N-[4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
2-furan-2-yl- acetamide Mass (M + H.sup.+): 439.2; .sup.1H NMR (500
MHz, DMSO-d.sub.6): .delta.1.4 8 (m, 2H), 1.63 (m, 2H), 3.04 (s,
3H), 3.08 (m, 2H), 3.41 (s, 2H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87
(s, 3H), 6.11 (d, 1H), 6.29 (s, 1H), 7.10 (s, 1H), 7.46 (d, 1H),
7.52 (s, 1H), 7.83 (t, 1H), 7.95 (t, 1H). Example 86 ##STR00125##
N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 2-phenyl- acetamide Mass (M +
H.sup.+): 449.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.47
(m, 2H), 1.62 (m, 2H), 3.04 (g, 2H), 3.06 (s, 3H), 3.27 (s, 2H),
3.47 (q, 2H), 3.81 (s, 3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.20 (m,
5H), 7.52 (s, 1H), 7.81 (t, 1H), 7.98 (t, 1H). Example 87
##STR00126## acetic acid-[4- (7,8-dimethoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- carbamoyl]-
methylester Mass (M + H.sup.+): 431.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.70 (m, 2H), 1.77 (m, 2H), 2.14 (s, 3H),
3.06 (s, 3H), 3.39 (q, 2H), 3.67 (q, 2H), 3.95 (d, 6H), 4.53 (s,
2H), 6.31 (brs, 1H), 6.45 (brs, 1H), 7.19 (s, 1H), 7.38 (s, 1H).
Example 88 ##STR00127## 1-tert-butyl-3-[4- (7,8-dimethoxy-
1-methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
urea Mass (M + H.sup.+): 430.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.15 (s, 9H), 1.40 (m, 2H), 1.60 (m, 2H),
2.95 (q, 2H), 3.03 (s, 3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s,
3H), 5.48 (s, 1H), 5.57 (t, 1H), 7.10 (s, 1H), 7.52 (s, 1H), 7.82
(t, 1H). Example 89 ##STR00128## 1-[4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
3-ethyl-urea Mass (M +
H.sup.+): 402.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.93
(t, 3H), 1.42 (m, 2H), 1.60 (m, 2H), 2.93 (q, 2H), 2.94 (q, 2H),
3.03 (s, 3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H), 5.65 (t,
1H), 5.73 (t, 1H), 7.10 (s, 1H), 7.52 (s, 1H), 7.81 (t, 1H).
Example 90 ##STR00129## 1-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-3- isopropylurea Mass (M +
H.sup.+): 416.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.96
(d, 6H), 1.40 (m, 2H), 1.60 (m, 2H), 2.98 (q, 2H), 3.03 (s, 3H),
3.48 (q, 2H), 3.58 (m, 1H), 3.82 (s, 3H), 3.87 (s, 3H), 5.51 (d,
1H), 5.62 (t, 1H), 7.11 (s, 1H), 7.52 (s, 1H), 7.81 (t, 1H).
Example 91 ##STR00130## 3-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 1,1-dimethyl- urea
Mass (M + H.sup.+): 402.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6):
.delta.1.45 (m, 2H), 1.60 (m, 2H), 2.71 (s, 6H), 2.99 (q, 2H), 3.03
(s, 3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.86 (s, 3H), 6.18 (t, 1H),
7.10 (s, 1H), 7.51 (s, 1H), 7.79 (t, 1H). Example 92 ##STR00131##
morpholine-4- carboxylic acid- [4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- amide Mass (M +
H.sup.+): 444.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.46
(m, 2H), 1.61 (m, 2H), 3.03 (q, 2H), 3.09 (s, 3H), 3.27 (m, 4H),
3.46 (m, 4H), 3.47 (q, 2H), 3.82 (s, 3H), 3.87 (s, 3H), 6.45 (t,
1H), 7.10 (s, 1H), 7.52 (s, 1H), 7.79 (t, 1H). Example 93
##STR00132## 1-cyclohexyl- 3-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- urea Mass (M +
H.sup.+): 456.3; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.01
(m, 3H), 1.25 (m, 2H), 1.41 (m, 2H), 1.45 (m, 1H), 1.60 (m, 5H),
1.66 (m, 2H), 2.97 (q, 2H), 3.03 (s, 3H), 3.48 (q, 2H), 3.82 (s,
3H), 3.87 (s, 3H), 5.57 (d, 1H), 5.63 (t, 1H) 7.10 (s, 1H), 7.51
(s, 1H), 7.82 (t, 1H). Example 94 ##STR00133## 1-4-7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- 3-phenyl-urea Mass (M + H.sup.+): 450.2; .sup.1H
NMR (500 MHz, DMSO-d.sub.6): .delta.1.50 (m, 2H), 1.66 (m, 2H),
3.03 (s, 3H), 3.10 (q, 2H), 3.51 (q, 2H), 3.81 (s, 3H), 3.87 (s,
3H), 6.08 (t, 1H), 6.84 (m, 1H), 7.10 (s, 1H), 7.15 (m, 2H), 7.31
(m, 2H), 7.52 (s, 1H) 7.85 (t, 1H), 8.32 (s, 1H). Example 95
##STR00134## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- benzamide Mass (M + H.sup.+):
435.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.56 (m, 2H),
1.64 (m, 2H), 3.03 (s, 3H), 3.20 (q, 2H), 3.49 (q, 2H), 3.82 (s,
3H), 3.87 (s, 3H), 7.09 (s, 1H), 7.46 (s, 1H), 7.52 (m, 1H), 7.64
(m, 2H), 7.72 (t, 1H), 7.90 (m, 2H), 9.37 (t, 1H). Example 96
##STR00135## 4-tert- butyl-N-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- benzamide Mass (M +
H.sup.+): 435.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.56
(m, 2H), 1.64 (m, 2H), 3.03 (s, 3H), 3.20 (q, 2H), 3.49 (q- 2H),
3.82 is, 3H), 3.87 (s, 3H), 7.09 (s, 1H), 7.46 (s, 1H), 7.52 (m,
1H), 7.64 (m, 2H), 7.72 (t, 1H), 7.90 (m, 2H), 9.37 (t, 1H).
Example 97 ##STR00136## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 2-methoxy-
benzamide Mass (M + H.sup.+): 491.3; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.23 (s, 9H), 1.57 (m, 2H), 1.67 (m, 2H),
3.02 (s, 3H), 3.26 (q, 2H), 3.50 (q, 2H), 3.79 (s, 3H), 3.86 (s,
3H), 7.08 (s, 1H), 7.39 (q, 2H), 7.50 (s, 1H), 7.70 (q, 2H), 7.82
(t, 1H), 8.31 (t, 1H). Example 98 ##STR00137## N-[4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- 4-fluoro- benzamide Mass (M + H.sup.+): 453.2;
.sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.59 (m, 2H), 1.68 (m,
2H), 3.03 (s, 3H), 3.26 (q, 2H), 3.51 (q, 2H), 3.80 (s, 3H), 3.86
(s, 3H), 7.08 (s, 1H), 7.23 (m, 2H), 7.51 (s, 1H), 7.84 (m, 3H),
8.43 (t, 1H). Example 99 ##STR00138## 2-chloro-N- [4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- benzamide Mass (M + H.sup.+): 469.2; .sup.1H NMR
(DMSO-d.sub.6): .delta.1.58 (m, 2H), 1.73 (m, 2H), 3.04 (s, 3H),
3.23 (q, 2H), 3.52 (q, 2H), 3.81 (s, 3H), 3.87 (s, 3H), 7.11 (s,
1H), 7.38 (m, 4H), 7.52 (s, 1H), 7.85 (t, 1H), 8.36 (t, 3H).
Example 100 ##STR00139## 4-chloro-N- [4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
benzamide Mass (M + H.sup.+): 469.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.58 (m, 2H), 1.68 (m, 2H), 3.03 (s, 3H),
3.27 (q, 2H), 3.51 (q, 2H), 3.80 (s, 3H), 3.87 (s, 3H), 7.08 (s,
1H), 7.45 (m, 2H), 7.47 (s, 1H), 7.78 (m, 2H), 7.80 (t, 1H), 8.48
(t, 1H). Example 101 ##STR00140## N-[4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
4-nitro- benzamide Mass (M + H.sup.+): 480.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.62 (m, 2H), 1.70 (m, 2H), 3.03 (s, 3H),
3.31 (q, 2H), 3.55 (q, 2H), 3.80 (s, 3H), 3.86 (s, 3H), 7.08 (s,
1H), 7.52 (s, 1H), 7.80 (t, 1H), 8.00 (q, 2H), 8.24 (q, 2H), 8.74
(t, 1H). Example 102 ##STR00141## 2,3- dichloro-N- [4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- benzamide Mass (M + H.sup.+): 504.1; .sup.1H NMR
(500 MHz, DMSO-d.sub.6): .delta.1.57 (m, 2H), 1.72 (m, 2H), 3.04
(s, 3H), 3.24 (q, 2H), 3.52 (q, 2H), 3.81 (s, 3H), 3.87 (s, 3H),
7.10 (d, 1H), 7.33 (m, 2H), 7.52 (s, 1H), 7.62 (d, 1H), 7.86 (t,
1H), 8.46 (t, 1H). Example 103 ##STR00142## N-[4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
isonicotinamide Mass (M + H.sup.+): 436.2; .sup.1H NMR (500 MHz,
CDC1.sub.3): .delta.1.81 (m, 2H), 1.85 (m, 2H), 3.06 (s, 3H), 3.58
(q, 2H), 3.71 (q, 2H), 3.90 (s, 3H), 3.95 (s, 3H), 6.24 (t, 1H),
6.83 (m, 1H), 7.14 (s, 1H), 7.40 (s, 1H), 7.60 (d, 1H), 8.67 (d,
1H). Example 104 ##STR00143## N-[4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
nicotinamide Mass (M + H.sup.+): 436.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.1.61 (m, 2H), 1.70 (m, 2H), 3.04 (s, 3H),
3.29 (q, 2H), 3.51 (q, 2H), 3.81 (s, 3H), 3.87 (s, 3H), 7.09 (s,
1H), 7.44 (m, 1H), 7.52 (s, 1H), 7.86 (t, 1H), 8.12 (d, 1H), 8.63
(t, 1H), 8.64 (d, 1H), 8.93 (s, 1H). Example 105 ##STR00144##
pyridine-2- carboxylic acid-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- amide Mass (M +
H.sup.+): 436.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.59
(m, 2H), 1.65 (m, 2H), 3.03 (s, 3H), 3.31 (q, 2H), 3.50 (q, 2H),
3.80 (s, 3H), 3.87 (s, 3H), 7.09 (s, 1H), 7.51 (s, 1H), 7.52 (m,
1H), 7.85 (t, 1H), 7.96 (m, 2H), 8.56 (d, 1H), 8.75 (t, 1H).
Example 106 ##STR00145## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 2-fluoro- benzamide
Mass (M + H.sup.+): 453.2, .sup.1H NMR (500 MHz, DMSO-d.sub.6):
.delta.1.58 (m, 2H), 1.69 (m, 2H), 3.04 (s, 3H), 3.31 (g, 2H), 3.81
(s, 3H), 3.87 (s, 3H), 4.17 (m, 2H), 7.10 (s, 1H), 7.19 (m, 1H),
7.21 (s, 1H), 7.45 (m, 1H), 7.52 (d, 1H), 7.63 (m, 1H), 7.85 (t,
1H), 8.25 (t, 1H). Example 107 ##STR00146## 6-chloro-N- [4-(7,8-
dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4-
ylamino)-butyl]- nicotinamide Mass (M + H.sup.+): 470.0; .sup.1H
NMR (500 MHz, DMSO-d.sub.6): .delta.1.60 (m, 2H), 1.70 (m, 2H),
3.03 (s, 3H), 3.30 (q, 2H), 3.52 (q, 2H), 3.81 (s, 3H), 3.87 (s,
3H), 7.07 (s, 1H), 7.51 (s, 1H), 7.57 (d, 1H), 7.82 (t, 1H), 8.15
(d, 1H), 8.66 (t, 1H), 8.76 (s, 1H). Example 108 ##STR00147##
2-chloro-N- [4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 6-methyl- nicotinamide Mass (M +
H.sup.+): 484.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.58
(m, 2H), 1.71 (m, 2H), 2.46 (s, 3H), 3.04 (s, 3H), 3.28 (q- 2H),
3.81 (s, 3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.25 (d, 1H), 7.52 (s,
1H), 7.69 (d, 1H), 7.85 (t, 1H), 8.44 (t, 1H). Example 109
##STR00148## N-[4-(7,8- dimethoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- methane- sulfonamide Mass (M +
H.sup.+): 409.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.53
(m, 2H), 1.66 (m, 2H), 2.84 (s, 3H), 2.96 (q, 2H), 3.02 (s, 3H),
3.48 (q, 2H), 3.82 (s, 3H), 3.86 (s, 3H), 6.91 (t, 1H), 7.48 (s,
1H), 7.82 (t, 1H). Example 110 ##STR00149## [4-(7,8- dimethoxy-1-
methyl-[1,2,4] triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]-
thiocarbamic acid-S- isopropylester Mass (M + H.sup.+): 433.2;
.sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.19 (d, 6H), 1.46 (m,
2H), 1.60 (m, 2H), 3.02 (s, 3H), 3.10 (q, 2H), 3.35 (m, 1H), 3.50
(q, 2H), 3.82 (s, 3H), 3.86 (s, 3H), 7.09 (s, 1H), 7.50 (s, 1H),
7.79 (t, 1H), 7.95 (t, 1H).
<Preparative Example 6> Preparation of
4-chloro-8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline
##STR00150##
[0999] Step 1: Preparation of
2,3-dichloro-7-fluoro-5-trifluoromethyl-quinoxaline
[1000] A
7-fluoro-5-trifluoromethyl-1,4-dihydro-quinoxaline-2,3-dione
compound (5.1 g, 20.3 mmol) was dissolved in 110 ml of chloroform,
to which 5 ml of dimethylformamide and thionylchloride (5 ml, 61.7
mmol) were added stepwise, followed by reflux-stirring for 3 hours.
The reaction was terminated by adding water at room temperature.
The precipitate was filtered, washed with water, and dried under
reduced pressure. As a result, 5.62 g of a target compound was
obtained (96% yield).
[1001] .sup.1H NMR (500 MHz, DMSO-d6): .delta.8.27 (d, 1H), 8.36
(d, 1H).
Step 2: Preparation of
(3-chloro-7-fluoro-5-trifluoromethyl-quinoxaline-2-yl)-hydrazine
[1002] 4.5 g of a target compound was obtained (84% yield) by the
same manner as described in step 2 of Preparative Example 5, except
that 2,3-dichloro-7-fluoro-5-trifluoromethyl-quinoxaline (5.39 g,
18.9 mmol) prepared in step 1 of Preparative Example 6 was
used.
[1003] Mass (M+H.sup.+): 281.0
[1004] .sup.1H NMR (500 MHz, DMSO-d6): .delta.7.20 (s, 1H), 7.36
(s, 1H).
Step 3: Preparation of
4-chloro-8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline
[1005] 1.4 g of a target compound was obtained (30% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
(3-chloro-7-fluoro-5-trifluoromethyl-quinoxaline-2-yl)-hydrazine
(4.45 g, 15.6 mmol) prepared in step 2 of Preparative Example 6 was
used.
[1006] Mass (M+H.sup.+): 305.0
[1007] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.10 (s, 3H), 8.07 (d,
1H), 8.09 (d, 1H).
<Example 111> Preparation of
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid-tert-butylester
##STR00151##
[1009] 1.55 g of a target compound was obtained (82% yield) by the
same manner as described in Example 1, except that
4-chloro-8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline (1.44 g, 4.72 mmol) prepared in step 3 of Preparative Example
6 was used.
[1010] Mass (M+H.sup.+): 457.2
[1011] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.42
(m, 2H), 1.61 (m, 2H), 2.93 (m, 2H), 2.97 (s, 3H), 3.51 (m, 2H),
3.87 (s, 3H), 6.74 (d, 1H), 7.05 (m, 1H), 7.20 (q, 1H), 7.67 (t,
1H), 7.97 (d, 1H).
<Example 112> Preparation of
N.sup.1-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl)-butane-1,4-diamine dihydrochloride
##STR00152##
[1013] 1.16 g of a target compound was obtained (76% yield) by the
same manner as described in Example 2, except that
[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino)-butyl]-carbamic acid-tert-butylester (1.42 g, 3.54
mmol) prepared in Example 111 was used.
[1014] Mass (M+H.sup.+): 357.1
[1015] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.60 (m, 2H), 1.70
(m, 2H), 2.73 (m, 2H), 3.01 (s, 3H), 3.52 (m, 2H), 6.04 (brs, 2H),
7.41 (d, 1H), 7.73 (s, 2H), 8.13 (d, 1H), 8.63 (t, 1H).
<Example 113> Preparation of
N-[4-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino)-butyl]-2,2-dimethyl-propionamide
##STR00153##
[1017] 56 mg of a target compound was obtained (80% yield) by the
same manner as described in Example 3, except that
N.sup.1-(8-fluoro-1-methyl-6-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl)-butane-1,4-diamine dihydrochloride (60 mg, 0.16 mmol)
prepared in Example 112 was used.
[1018] Mass (M+H.sup.+): 441.2
[1019] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.01 (s, 9H), 1.43 (s,
2H), 1.60 (s, 2H), 2.99 (s, 5H), 3.49 (s, 2H), 7.36 (s, 1H), 7.68
(d, 1H), 8.10 (d, 1H), 8.59 (s, 1H).
[1020] The compounds shown in Table 6 below were prepared by the
same manner as described in Example 113.
TABLE-US-00006 TABLE 6 Example Structure Name Data Example 114
##STR00154## [4-(8-fluoro-1- methyl-6- trifluoromethyl-
[1,2,4]triazolo [4,3-a]quinoxaline- 4-ylamino)- butyl]-carbamic
acid isopropylester Mass (M + H.sup.+): 143.2; .sup.1H NMR (500
MHz, DMSO-d.sub.6): .delta.1.09 (s, 6H), 1.43 (m, 2H), 1.62 (m,
2H), 2.94 (m, 2H), 3.00 (s, 3H), 3.51 (m, 2H), 4.68 (s, 1H), 6.92
(t, 1H), 7.72 (d, 1H), 8.13 (d, 1H), 8.60 (t, 1H) Example 115
##STR00155## [4-(8-fluoro-1- methyl-6- trifluoromethyl-
[1,2,4]triazolo [4,3-a]quinoxaline- 4-ylamino)-butyl]- carbamic
acid isobutylester Mass (M + H.sup.+): 157.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.0.87 (s, 9H), 1.40 (m, 2H), 1.62 (m, 2H),
1.86 (s, 2H), 3.00 (s, 5H), 3.28 (s, 1H), 3.51 (m, 2H), 7.63 (s,
1H), 7.69 (d, 1H), 8.10 (d, 1H), 8.59 (m, 1H) Example 116
##STR00156## N-[4-(8-fluoro-1- methyl-6- trifluoromethyl-
[1,2,4]triazolo [4,3-a]quinoxaline- 4-ylamino)-butyl]-
3,3-dimethyl- butyramide Mass (M + H.sup.+): 455.2; .sup.1H NMR
(500 MHz, DMSO-d.sub.6): .delta.0.80 (d, 6H), 1.42 (m, 2H), 1.61
(m, 2H), 1.75 (m, 1H), 2.94 (m, 2H), 2.99 (s, 3H), 3.40 (m, 2H),
3.64 (m, 2H), 6.99 (m, 1H), 7.70 (d, 1H), 8.11 (d, 1H), 8.58 (m,
1H)
<Preparative Example 7> Preparation of
4-chloro-6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00157##
[1021] Step 1: Preparation of
2,3-dichloro-5-methoxy-quinoxaline
[1022] 1.85 g of a target compound was obtained (89% yield) by the
same manner as described in step 1 of Preparative Example 5, except
that 5-methoxy-1,4-dihydro-quinoxaline-2,3-dione (1.75 g, 9.1 mmol)
was used.
[1023] Mass (M+H.sup.+): 229.0
[1024] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.98 (s, 3H), 7.36 (d,
1H), 7.54 (d, 1H), 7.80 (m, 1H).
Step 2: Preparation of
(3-chloro-5-methoxy-quinoxaline-2-yl)-hydrazine
[1025] 270 mg of a target compound was obtained (33% yield) by the
same manner as described in step 2 of Preparative Example 5, except
that 2,3-dichloro-5-methoxy-quinoxaline (830 mg, 3.62 mmol)
prepared in step 1 of Preparative Example 7 was used.
[1026] Mass (M+H.sup.+): 225.0
[1027] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.87 (s, 3H), 6.85
(d, 1H), 7.17 (d, 1H), 7.47 (t, 1H), 8.77 (s, 1H).
Step 3: Preparation of
4-chloro-6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1028] 260 mg of a target compound was obtained (87% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that (3-chloro-5-methoxy-quinoxaline-2-yl)-hydrazine (270 mg, 1.2
mmol) prepared in step 2 of Preparative Example 7 was used.
[1029] Mass (M+H.sup.+): 249.0
[1030] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.05 (s, 3H), 3.96
(s, 3H), 7.28 (d, 1H), 7.69 (t, 1H), 7.87 (d, 1H).
<Example 117> Preparation of
[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00158##
[1032] 350 mg of a target compound was obtained (89% yield) by the
same manner as described in Example 1, except that
4-chloro-6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (242
mg, 0.97 mmol) prepared in step 3 of Preparative Example 7 was
used.
[1033] Mass (M+H.sup.+): 401.2
[1034] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.42 (m,
2H), 1.61 (m, 2H), 2.93 (m, 2H), 2.97 (s, 3H), 2.99 (m, 2H), 3.50
(m, 2H), 3.88 (s, 3H), 6.73 (m, 1H), 7.02 (m, 1H), 7.19 (m, 1H),
7.65 (m, 1H), 7.97 (d, 1H).
<Example 118> Preparation of
N.sup.1-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine dihydrochloride
##STR00159##
[1036] 240 mg of a target compound was obtained (74% yield) by the
same manner as described in Example 2, except that
[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester (350 mg, 0.87 mmol) prepared in
Example 117 was used.
[1037] Mass (M+H.sup.+): 301.2
[1038] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.63 (s, 2H), 1.72
(s, 2H), 2.94 (m, 2H), 3.00 (s, 3H), 3.57 (s, 2H), 3.91 (s, 3H),
5.88 (brs, 2H), 7.10 (s, 1H), 7.25 (s, 1H), 7.70 (d, 1H), 7.92 (s,
2H), 8.26 (s, 1H).
<Example 119> Preparation of
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide
##STR00160##
[1040] 59 mg of a target compound was obtained (80% yield) by the
same manner as described in Example 59, except that
N.sup.1-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine dihydrochloride (60 mg, 0.16 mmol) prepared in
Example 118 was used.
[1041] Mass (M+H.sup.+): 385.2
[1042] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.14 (s, 9H), 1.65
(m, 2H), 1.75 (m, 2H), 3.04 (s, 3H), 3.33 (q, 2H), 3.75 (q, 2H),
3.98 (s, 3H), 5.94 (s, 1H), 4.60 (m, 1H), 6.94 (d, 1H), 7.17 (m,
1H), 7.55 (m, 1H)
<Example 120> Preparation of
N-[4-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-carbamic acid isobutylester
##STR00161##
[1044] 46 mg of a target compound was obtained (75% yield) by the
same manner as described in Example 53, except that
N.sup.1-(6-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine dihydrochloride (60 mg, 0.16 mmol) prepared in
Example 118 was used.
[1045] Mass (M+H.sup.+): 401.2
[1046] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.45 (m,
2H), 1.75 (m, 2H), 1.96 (m, 1H), 2.97 (s, 3H), 2.99 (m, 2H), 3.53
(m, 2H), 3.65 (m, 2H), 3.87 (s, 3H), 7.04 (m, 1H), 7.06 (m, 1H),
7.19 (m, 1H), 7.67 (d, 1H), 7.98 (m, 1H).
<Preparative Example 8> Preparation of
4-chloro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00162##
[1047] Step 1: Preparation of
2,3-dichloro-6-methoxy-quinoxaline
[1048] 6-Methoxy-1,4-dihydro-quinoxaline-2,3-dione (15.5 g, 81
mmol) was dissolved in 75 ml of phosphorusoxychloride, followed by
reflux stirring for 24 hours. The reaction was terminated using
water and methanol (1:1 solution) at 0.about.5.degree. C. The
resulting precipitate was filtered and dried under reduced
pressure. As a result, 17.2 g of a target compound was obtained
(93% yield).
[1049] Mass (M+H.sup.+): 229.2
[1050] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.93 (s, 3H), 7.46
(s, 1H), 7.54 (d, 1H), 7.96 (d, 1H).
Step 2: Preparation of
2-chloro-6-methoxy-3-hydrazinylquinoxaline
[1051] A target compound was obtained (quantitative yield) by the
same manner as described in step 2 of Preparative Example 5, except
that 2,3-dichloro-6-methoxy-quinoxaline (750 mg, 3.00 mmol)
prepared in step 1 of Preparative Example 8 was used.
[1052] Mass (M+H.sup.+): 225.2
Step 3: Preparation of
4-chloro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1053] 756 mg of a target compound was obtained (88% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that 2-chloro-6-methoxy-3-hydrazinylquinoxaline (780 mg, 3.47 mmol)
prepared in step 2 of Preparative Example 8 was used.
[1054] Mass (M+H.sup.+): 249.0
[1055] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.11 (s, 3H), 3.96
(s, 3H), 7.30 (s, 1H), 7.66 (d, 1H), 7.92 (d, 1H).
<Example 121> Preparation of
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00163##
[1057] 3.9 g of a target compound was obtained (82% yield) by the
same manner as described in Example 57, except that
4-chloro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (3 g,
12 mmol) prepared in step 3 of Preparative Example 8 was used.
[1058] Mass (M+H.sup.+): 401.2
[1059] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.60 (m, 2H), 2.92 (q, 2H), 3.02 (s, 3H), 3.46 (q, 2H), 3.84
(s, 3H), 6.74 (t, 1H), 7.07 (d, 1H), 7.78 (t, 1H)
<Example 122> Preparation of
N.sup.1-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid
##STR00164##
[1061] 2 g of a target compound was obtained (76% yield) by the
same manner as described in Example 58, except that
[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester (3 g, 7.5 mmol) prepared in Example
121 was used.
[1062] Mass (M+H.sup.+): 301.2
[1063] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, H), 1.68 (m,
2H), 2.80 (q, 2H), 3.03 (s, 3H), 3.51 (s, 3H), 3.51 (q, 2H), 3.85
(s, 3H), 7.08 (d, 1H), 7.50 (m, 2H), 7.52 (brs, 2H), 7.90 (brs,
1H).
<Example 123> Preparation of
N-[4-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide
##STR00165##
[1065] 175 mg of a target compound was obtained (90% yield) by the
same manner as described in Example 59, except that
N.sup.1-(8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid (250 mg, 0.83 mmol) prepared
in Example 122 was used.
[1066] Mass (M+H.sup.+): 385.2
[1067] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.46
(m, 2H), 1.60 (m, 2H), 1.60 (m, 2H), 3.02 (s, 3H), 3.04 (q, 2H),
3.45 (q, 2H), 3.84 (s, 3H), 7.07 (d, 1H), 7.36 (t, 1H), 7.49 (s,
1H), 7.51 (d, 1H), 7.78 (t, 1H).
[1068] The compounds shown in Table 7 below were prepared by the
same manner as described in Example 123.
TABLE-US-00007 TABLE 7 Example Structure Name Data Example 124
##STR00166## [4-(8-methoxy-1- methyl-[1,2,4] triazolo[4,3-a]
quinoxaline-4- ylamino)-butyl]- 3,3-dimethyl- butyramide Mass (M +
H.sup.+): 399.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.0.88
(s, 9H), 1.45 (m, 2H), 1.63 (m, 2H), 1.87 (s, 2H), 3.00 (s, 3H),
3.03 (q, 2H), 3.47 (q, 2H), 3.84 (s, 3H), 7.07 (d, 1H), 7.50 (s,
1H), 7.51 (d, 1H), 7.62 (t, 1H), 7.79 (t, 1H). Example 125
##STR00167## 2-(R)-hydroxy-N- [4-(8-methoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 3-methyl-
butyramide Mass (M + H.sup.+): 401.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.0.69 (d, 3H), 0.83 (d, 3H), 1.48 (m, 2H),
1.61 (m, 2H), 1.91 (m, 1H), 3.02 (s, 3H), 3.12 (m, 2H), 3.47 (m,
2H), 3.57 (m, 1H), 3.84 (s, 3H), 5.22 (d, 1H), 7.07 (d, 1H), 7.50
(d, 1H), 7.51 (s, 1H), 7.62 (t, 1H), 7.80 (t, 1H). Example 126
##STR00168## 2-(S)-hydroxy-N- [4-(8-methoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- 3-methyl-
butyramide Mass (M + H.sup.+): 401.2; .sup.1H NMR (500 MHz,
DMSO-d.sub.6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.48 (m, 2H),
1.61 (m, 2H), 1.91 (m, 1H), 3.02 (s, 3H), 3.10 (m, 2H), 3.47 (m,
2H), 3.59 (m, 1H), 3.93 (s, 1H), 3.93 (s, 3H), 5.22 (d, 1H), 7.07
(d, 1H), 7.50 (d, 1H), 7.51 (s, 1H), 7.63 (t, 1H), 7.80 (t, 1H).
Example 127 ##STR00169## N-[4-(8-methoxy- 1-methyl-[1,2,4]
triazolo[4,3-a] quinoxaline-4- ylamino)-butyl]- benzamide Mass (M +
H.sup.+): 405.2; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.57
(m, 2H), 1.69 (m, 2H), 3.01 (s, 3H), 3.26 (q, 2H), 3.52 (q, 2H),
3.83 (s, 3H), 7.06 (d, 1H), 7.38 (m, 2H), 7.40 (m, 1H), 7.48 (m,
2H), 7.76 (m, 2H), 7.78 (t, 1H), 8.39 (t, 1H). Example 128
##STR00170## 2-chloro-N-[4-(8- methoxy-1-methyl- [1,2,4]triazolo
[4,3-a]quinoxaline- 4-ylamino)-butyl]- benzamide Mass (M +
H.sup.+): 439.0; .sup.1H NMR (500 MHz, DMSO-d.sub.6): .delta.1.58
(m, 2H), 1.71 (m, 2H), 3.02 (s, 3H), 3.27 (q, 2H), 3.51 (q, 2H),
3.85 (s, 3H), 7.08 (d, 1H), 7.34 (m, 4H), 7.53 (m, 2H), 7.82 (t,
1H), 8.36 (t, 1H). Example 129 ##STR00171## 2-chloro-N-[4-(8-
methoxy-1-methyl- [1,2,4]triazolo[4,3-a] quinoxaline-4-
ylamino)-6-methyl- nicotinamide Mass (M + H.sup.+): 454.2; .sup.1H
NMR (500 MHz, DMSO-d.sub.6): .delta.1.57 (m, 2H), 1.70 (m, 2H),
2.40 (s, 3H), 3.02 (s, 3H), 3.23 (q, 2H), 3.50 (q, 2H), 3.84 (s,
3H), 7.07 (d, 1H), 7.25 (d, 1H), 7.51 (m, 2H), 7.68 (d, 1H) 7.82
(t, 1H), 8.43 (t, 1H).
<Preparative Example 9> Preparation of
6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00172##
[1070] 6-Methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline was
obtained by the same manner as described in Preparative Example 5,
except that 5-methoxy-6-methyl-1,4-dihydro-quinoxaline-2,3-dione
was used.
Step 1: Preparation of
2,3-dichloro-5-methoxy-6-methyl-quinoxaline
[1071] Mass (M+H.sup.+): 243.0
[1072] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.41 (s, 3H), 3.98 (s,
3H), 7.71 (d, 1H), 7.77 (d, 1H).
Step 2: Preparation of
3-chloro-5-methoxy-6-methyl-quinoxaline-2-ylhydrazine
[1073] Mass (M+H.sup.+): 239.1
Step 3: Preparation of
4-chloro-6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1074] Mass (M+H.sup.+): 263.0
[1075] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.35 (s, 3H), 3.03
(s, 3H), 3.96 (s, 3H), 7.60 (d, 1H), 7.96 (d, 1H)
<Example 130> Preparation of
{4-[6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-b-
utyl}-carbamic acid-tert-butylester
##STR00173##
[1077] 1.52 g of a target compound was obtained (92% yield) by the
same manner as described in Example 57, except that
4-chloro-6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
(1.05 g, 4.00 mmol) prepared in step 3 of Preparative Example 9 was
used.
[1078] Mass (M+H.sup.+): 415.2
[1079] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.44 (q,
2H), 1.63 (q, 2H), 2.26 (s, 3H), 2.92 (q, 2H), 2.94 (s, 3H), 3.53
(q, 2H), 3.94 (s, 3H), 6.73 (t, 1H), 7.08 (d, 1H), 7.71 (d, 1H),
8.12 (t, 1H).
<Example 131> Preparation of
N.sup.1-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid
##STR00174##
[1081] 1.4 g of a target compound was obtained (71% yield) by the
same manner as described in Example 58, except that
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester (1.5 g, 3.62 mmol) prepared in
Example 130 was used.
[1082] Mass (M+H.sup.+): 315.2
[1083] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.61 (m, 2H), 1.71 (m,
2H), 2.27 (s, 3H), 2.81 (m, 2H), 2.96 (s, 3H), 3.58 (q, 2H), 3.95
(s, 3H), 7.10 (d, 1H), 7.61 (brm, 2H), 7.73 (d, 1H), 8.19 (t,
1H).
<Example 132> Preparation of
[4-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-2,2-dimethyl-propionamide
##STR00175##
[1085] 52 mg of a target compound was obtained (60% yield) by the
same manner as described in Example 59, except that
N.sup.1-(6-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid (120 mg, 0.22 mmol)
prepared in Example 131 was used.
[1086] Mass (M+H.sup.+): 399.1
[1087] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.01 (s, 9H), 1.46 (q,
2H), 1.63 (m, 2H), 2.26 (s, 3H), 2.95 (s, 3H), 3.04 (q, 2H), 3.54
(q, 2H), 3.94 (s, 3H), 7.08 (d, 1H), 7.36 (t, 1H), 7.71 (d, 1H),
8.13 (t, 1H).
[1088] The compounds shown in Table 8 below were prepared by the
same manner as described in Example 132.
TABLE-US-00008 TABLE 8 Example Structure Name Data Example 133
##STR00176## [4-(6- methoxy- 1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid isopropylester Mass
(M + H.sup.+): 401.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.09
(d, 6H), 1.46 (m, 2H), 1.64 (m, 2H), 2.27 (s, 3H), 2.95 (s, 3H),
2.96 (m, 2H), 3.53 (q, 2H), 3.94 (s, 3H), 4.67 (m, 1H), 6.93 (t,
1H), 7.08 (d, 1H), 7.72 (d, 1H), 8.13 (t, 1H). Example 134
##STR00177## [4-(6- methoxy- 1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81
(d, 6H), 1.46 (m, 2H), 1.64 (m, 2H), 1.75 (m, 1H), 2.26 (s, 3H),
2.94 (s, 3H), 2.99 (q, 2H), 3.53 (q, 2H), 3.65 (d, 2H), 3.94 (s,
3H). 7.02 (t, 1H), 7.08 (d, 1H), 7.70 (d, 1H), 8.13 (t, 1H).
Example 135 ##STR00178## N-[4-(6- methoxy- 1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]-3- methyl-
butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.78 (d, 6H), 1.44 (m, 2H), 1.64 (m, 2H), 1.85 (d,
2H), 1.89 (m, 1H), 2.26 (s, 3H), 2.95 (s, 3H), 3.04 (m, 2H), 3.53
(m, 2H), 3.94, (s, 3H), 7.08 (d, 1H), 7.69 (m + d, 2H), 8.13 (t,
1H). Example 136 ##STR00179## 2-(R)- hydroxy-N- [4-(6- methoxy-
1,7- dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)-
butyl]-3- methyl- butyramide Mass (M + H.sup.+): 415.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.72 (d, 3H), 0.85 (d, 3H), 1.54 (m,
2H), 1.68 (m, 2H), 1.92 (m, 1H), 2.28 (s, 3H), 2.95 (s, 3H), 3.12
(m, 2H), 3.59 (m, 3H), 3.97 (s, 3H), 4.98 (d, 1H), 7.08 (d, 1H),
7.46 (t, 1H), 7.70 (d, 1H), 7.88 (t, 1H). Example 137 ##STR00180##
2-(S)- hydroxy-N- [4-(6- methoxy- 1,7- dimethyl- [1,2,4]triazolo
[4,3-a] quinoxaline-4- ylamino)- butyl]-3- methyl- butyramide Mass
(M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.72
(d, 3H), 0.85 (d, 3H), 1.54 (m, 2H), 1.68 (m, 2H), 1.92 (m, 1H),
2.28 (s, 3H), 2.95 (s, 3H), 3.12 (m, 2H), 3.59 (m, 3H), 3.97 (s,
3H), 4.98 (d, 1H), 7.08 (d, 1H), 7.46 (t, 1H), 7.70 (d, 1H), 7.88
(t, 1H). Example 138 ##STR00181## N-[4-(6- methoxy- 1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 419.1; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.60 (m, 2H), 1.70 (m, 2H), 2.25 (s, 3H), 2.94 (s, 3H), 3.27
(q, 2H), 3.57 (q, 2H), 3.91 (s, 3H), 7.07 (d, 1H), 7.38 (t, 2H),
7.44 (d, 1H), 7.69 (d, 1H), 7.76 (d, 2H), 8.15 (t, 1H), 8.39 (t,
1H). Example 139 ##STR00182## 2-fluoro-N- [4-(6- methoxy- 1,7-
dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]-
benzamide Mass (M + H.sup.+): 437.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.58 (m, 2H), 1.72 (m, 2H), 2.26 (s, 3H), 2.95 (s,
3H), 3.26 (m, 2H), 3.58 (m, 2H), 3.93 (s, 3H), 7.08 (d, 1H), 7.19
(m, 2H), 7.44 (m, 1H), 7.52 (t, 1H), 7.71 (d, 1H), 8.16 (t, 1H).
Example 140 ##STR00183## 2-chloro-N- [4-(6- methoxy- 1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 453.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.59 (m, 2H) 1.74 (m, 2H), 2.27 (s, 3H), 2.95 (s, 1H), 3.24
(q, 2H), 3.59 (q, 2H), 3.95 (s, 3H), 7.09 (d, 1H), 7.29 (t, 1H),
7.32 (m, 1H), 7.35 (m, 1H), 7.38 (m, 1H), 7.42 (d, 1H), 7.71 (d,
1H), 8.16 (t, 1H), 8.35 (t, 1H). Example 141 ##STR00184##
2-chloro-N- [4-(6- methoxy- 1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]-6- methyl- nicotinamide Mass (M +
H.sup.+): 468.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m,
2H), 1.74 (m, 2H), 2.26 (s, 3H), 2.42 (s, 3H), 2.95 (s, 3H), 3.23
(q, 2H), 3.58 (q, 2H), 3.95 (s, 3H), 7.09 (d, 1H), 7.24 (d, 1H),
7.68 (d, 1H), 7.71 (d, 1H), 8.16 (t, 1H), 8.43 (t, 1H).
<Preparative Example 10> Preparation of
4-chloro-6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline
##STR00185##
[1090]
4-Chloro-6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a-
]quinoxaline was obtained by the same manner as described in
Preparative Example 5, except that
5-methoxy-7-trifluoromethyl-1,4-dihydro-quinoxaline-2,3-dione was
used.
Step 1: Preparation of
2,3-dichloro-5-methoxy-7-trifluoromethyl-quinoxaline
[1091] .sup.1H NMR (500 MHz, DMSO-d6): .delta.4.07 (s, 3H), 7.53
(s, 1H), 7.96 (s, 1H).
Step 2: Preparation of
(3-chloro-5-methoxy-7-trifluoromethyl-quinoxaline-2-yl)-hydrazine
[1092] Mass (M+H.sup.+): 293.0
Step 3: Preparation of
4-chloro-6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline
[1093] Mass (M+H.sup.+): 317.0
[1094] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.10 (s, 3H), 4.06 (s,
3H), 7.57 (s, 1H), 8.01 (s, 1H).
[1095] The compounds shown in Table 9 below were prepared by using
4-chloro-6-methoxy-1-methyl-8-trifluoromethyl-[1,2,4]triazolo[4,3-a]quino-
xaline prepared by the same manner as described in Preparative
Example 10 as an intermediate.
TABLE-US-00009 TABLE 9 Example Structure Name Data Example 142
##STR00186## [4-(6- methoxy-1- methyl-8- trifluoromethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 496.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.43 (m, 2H), 1.62 (m, 2H),
2.92 (m, 2H), 3.01 (s, 3H), 3.54 (m, 2H), 3.95 (s, 3H), 6.73 (t,
1H), 7.28 (s, 1H), 7.85 (s, 1H), 8.44 (t, 1H). Example 143
##STR00187## N.sup.1-(6- methoxy-1- methyl-8- trifluoromethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4-yl)- butane-1,4- diamine
ditrifluoroacetic acid Mass (M + H.sup.+): 369.1; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.70 (m, 2H), 2.85 (m, 2H),
3.02 (s, 3H), 3.59 (m, 2H), 3.96 (s, 3H), 7.29 (s, 1H), 7.62 (brm,
2H), 7.86 (s, 1H), 8.51 (t, 1H). Example 144 ##STR00188## [4-(6-
methoxy-1- methyl-8- trifluoromethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid isopropylester Mass
(M + H.sup.+): 455.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.09
(d, 6H), 1.43 (m, 2H), 1.63 (m, 2H), 2.97 (q, 2H), 3.01 (s, 3H),
3.55 (q, 2H), 3.95 (s, 3H), 4.68 (m, 1H), 6.93 (t, 1H), 7.28 (s,
1H). 7.85 (s, 1H), 8.44 (t, 1H). Example 145 ##STR00189## N-[4-(6-
methoxy-1- methyl-8- trifluoromethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- 3- methyl- butyramide Mass (M +
H.sup.+): 453.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
6H), 1.44 (m, 2H), 1.64 (m, 2H), 1.87 (m, 1H), 1.87 (d, 2H), 3.01
(s, 3H), 3.05 (q, 2H), 3.55 (m, 2H), 3.95 (s, 3H), 7.28 (s, 1H),
7.68 (t, 1H), 7.85 (s, 1H), 8.45 (t, 1H).
<Preparative Example 11> Preparation of
4-chloro-8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00190##
[1097]
4-Chloro-8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
was obtained by the same manner as described in Preparative Example
5, except that 6-methoxy-7-methyl-1,4-dihydro-quinoxaline-2,3-dione
was used.
Step 1: Preparation of
2,3-dichloro-6-methoxy-7-methyl-quinoxaline
[1098] Mass (M+H.sup.+): 243.0
[1099] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.35 (s, 3H), 3.96 (s,
3H), 7.41 (s, 1H), 7.83 (s, 1H).
Step 2: Preparation of
(3-chloro-7-methoxy-6-methyl-quinoxaline-2-yl)-hydrazine
[1100] Mass (M+H.sup.+): 239.1
[1101] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.21 (s, 3H), 3.87 (s,
3H), 4.48 (brs, 2H), 7.02 (s, 1H), 7.47 (s, 1H), 8.55 (s, 1H).
Step 3: Preparation of
4-chloro-8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1102] Mass (M+H.sup.+): 263.0
[1103] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.27 (s, 3H), 3.15
(s, 3H), 4.02 (s, 3H), 7.63 (s, 1H), 7.79 (s, 1H)
<Example 146> Preparation of
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester
##STR00191##
[1105] 1.80 g of a target compound was obtained (84% yield) by the
same manner as described in Example 57, except that
4-chloro-8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
(1.35 g, 5.14 mmol) prepared in step 3 of Preparative Example 11
was used.
[1106] Mass (M+H.sup.+): 415.2
[1107] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.42 (q,
2H), 1.59 (m, 2H), 2.19 (s, 3H), 2.92 (q, 2H), 3.04 (s, 3H), 3.44
(q, 2H), 3.89 (s, 3H), 6.75 (t, 1H), 7.38 (s, 1H), 7.44 (s, 1H),
7.73 (t, 1H).
<Example 147> Preparation of
N.sup.1-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid
##STR00192##
[1109] 1.4 g of a target compound was obtained (71% yield) by the
same manner as described in Example 58, except that
[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester (1.5 g, 3.62 mmol) prepared in
Example 146 was used.
[1110] Mass (M+H.sup.+): 315.1
[1111] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.58 (m, 2H), 1.67 (m,
2H), 2.21 (s, 3H), 2.80 (m, 2H), 3.07 (s, 3H), 3.50 (q, 2H), 3.90
(s, 3H), 7.39 (s, 1H), 7.48 (s, 1H), 7.60 (brs, 2H), 7.86 (brs,
1H).
<Example 148> Preparation of
N-[4-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-2,2-dimethyl-propionamide
##STR00193##
[1113] 52 mg of a target compound was obtained (60% yield) by the
same manner as described in Example 59, except that
N.sup.1-(8-methoxy-1,7-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid (120 mg, 0.22 mmol)
prepared in Example 147 was used.
[1114] Mass (M+H.sup.+): 399.1
[1115] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.01 (s, 9H), 1.46 (q,
2H), 1.63 (m, 2H), 2.26 (s, 3H), 2.95 (s, 3H), 3.04 (q, 2H), 3.54
(q, 2H), 3.94 (s, 3H), 7.08 (d, 1H), 7.36 (t, 1H), 7.71 (d, 1H),
8.13 (t, 1H).
[1116] The compounds shown in Table 10 below were prepared by the
same manner as described in Example 148.
TABLE-US-00010 TABLE 10 Example Structure Name Data Example 149
##STR00194## [4-(8- methoxy-1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid isopropylester Mass
(M + H.sup.+): 401.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.09
(d, 6H), 1.44 (m, 2H), 1.59 (m, 2H), 2.19 (s, 3H), 2.95 (q, 2H),
3.05 (s, 3H), 3.45 (q, 2H), 3.89 (s, 3H), 4.68 (m, 1H), 6.94 (t,
1H), 7.39 (s, 1H), 7.46 (s, 1H), 7.74 (t, 1H). Example 150
##STR00195## [4-(8- methoxy-1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81
(d, 6H), 1.43 (m, 2H), 1.60 (m, 2H), 1.76 (m, 1H), 2.20 (s, 3H),
2.97 (q, 2H), 3.05 (s, 3H), 3.45 (q, 2H), 3.66 (d, 1H), 3.89 (s,
3H), 7.03 (t, 1H), 7.40 (s, 1H), 7.47 (s, 1H), 7.75 (t, 1H).
Example 151 ##STR00196## N-[4-(8- methoxy-1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]-3- methyl-
butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 1.44 (m, 2H), 1.60 (m, 2H), 1.86 (m,
2H), 1.91 (m. 1H), 2.20 (s, 3H), 3.03 (q, 2H), 3.05 (s, 3H), 3.90
(s, 3H), 7.39 (s, 1H), 7.47 (s, 1H), 7.69 (t, 1H), 7.75 (t, 1H) .
Example 152 ##STR00197## 2-(R)- hydroxy-N- [4-(8- methoxy-1,7-
dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)-
butyl]-3- methyl- butyramide Mass (M + H.sup.+): 415.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.46 (m,
2H), 1.60 (m, 2H), 1.91 (m, 1H), 2.21 (s, 3H), 3.03 (s, 3H), 3.15
(q, 2H), 3.45 (q, 2H), 3.60 (d, 1H), 5.23 (d, 1H), 7.36 (s, 1H),
7.41 (s, 1H), 7.75 (t, 1H), 7.94 (t, 1H). Example 153 ##STR00198##
2-(S)- hydroxy-N- [4-(8- methoxy-1,7- dimethyl- [1,2,4]triazolo
[4,3-a] quinoxaline-4- ylamino)- butyl]-3- methyl- butyramide Mass
(M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68
(d, 3H), 0.83 (d, 3H), 1.46 (m, 2H), 1.60 (m, 2H), 1.91 (m, 1H),
2.21 (s, 3H), 3.03 (s, 3H), 3.15 (q, 2H), 3.45 (q, 2H), 3.60 (d,
1H), 5.23 (d, 1H), 7.36 (s, 1H), 7.41 (s, 1H), 7.75 (t, 1H), 7.94
(t, 1H). Example 154 ##STR00199## N-[4-(8- methoxy-1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 419.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.57 (m, 2H), 1.68 (m, 2H), 2.18 (s, 3H), 3.05 (s, 3H), 3.27
(m, 2H), 3.49 (q, 2H), 3.89 (s, 3H), 7.39 (m, 3H), 7.46 (m, 2H),
7.77 (m, 3H), 8.40 (t, 1H). Example 155 ##STR00200## 2-fluoro-N-
[4-(8- methoxy-1,7- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- benzamide Mass (M + H.sup.+):
437.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.57 (m, 2H), 1.69
(m, 2H), 2.19 (s, 3H), 3.05 (s, 3H), 3.24 (m, 2H), 3.50 (q, 2H),
3.89 (s, 3H), 7.19 (m, 1H), 7.22 (d, 1H), 7.39 (s, 1H), 7.34 (m,
1H), 7.47 (s, 1H), 7.53 (t, 1H), 7.77 (t, 1H), 8.25 (t, 1H).
Example 156 ##STR00201## 2-chloro-N- [4-(8- methoxy-1,7- dimethyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 453.1; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.56 (m, 2H), 1.70 (m, 2H), 2.19 (s, 3H), 3.05 (s, 3H), 3.23
(m, 2H), 3.49 (m, 2H), 3.89 (s, 3H), 7.28 (m, 1H), 7.33 (m, 1H),
7.34 (m, 1H), 7.40 (m, 2H), 7.46 (m, 1H), 7.78 (t, 1H), 8.35 (t,
1H). Example 157 ##STR00202## 2-chloro-N- [4-(8- methoxy-1,7-
dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)-
butyl]-6- methyl nicotinamide Mass (M + H.sup.+): 468.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.57 (m, 2H), 1.70 (m, 2H), 2.20 (s,
3H), 2.41 (s, 3H), 3.06 (s, 3H), 3.24 (q, 2H), 3.49 (q, 2H), 3.90
(s, 3H), 7.24 (d, 1H), 7.39 (s, 1H), 7.47 (s, 1H), 7.68 (d, 1H),
7.79 (t, 1H), 8.43 (t, 1H).
<Preparative Example 12> Preparation of
4-chloro-8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00203##
[1118]
4-Chloro-8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
was obtained by the same manner as described in Preparative Example
5, except that 6-methoxy-8-methyl-1,4-dihydro-quinoxaline-2,3-dione
was used.
Step 1: Preparation of
2,3-dichloro-7-methoxy-5-methyl-quinoxaline
[1119] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.46 (s, 3H), 3.89 (s,
3H), 7.25 (s, 1H), 7.40 (s, 1H).
Step 2: Preparation of
(3-chloro-7-methoxy-5-methyl-quinoxaline-2-yl)-hydrazine
[1120] Mass (M+H.sup.+): 239.1
Step 3: Preparation of
4-chloro-8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1121] Mass (M+H.sup.+): 263.2
[1122] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.59 (s, 3H), 3.09 (s,
3H), 3.93 (s, 3H), 7.22 (s, 1H), 7.51 (s, 1H).
[1123] The compounds shown in Table 11 below were prepared by using
4-chloro-8-methoxy-1,6-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared by the same manner as described in Preparative Example 12
as an intermediate.
TABLE-US-00011 TABLE 11 Example Structure Name Data Example 158
##STR00204## [4-(8- methoxy-1,6- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl]- carbamic acid-tert- butylester
Mass (M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.31 (s, 9H), 1.44 (m, 2H), 1.63 (m, 2H), 2.47 (s, 3H), 2.92
(q, 2H), 3.00 (s, 3H), 3.49 (q, 2H), 3.82 (s, 3H), 6.73 (t, 1H),
7.00 (s, 1H), 7.37 (s, 1H), 7.80 (t, 1H). Example 159 ##STR00205##
N.sup.1-(8- methoxy-1,6- dimethyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4-yl)- butane-1,4- diamine ditrifluoroacetic acid Mass
(M + H.sup.+): 315.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.61
(m, 2H), 1.71 (m, 2H), 2.50 (s, 3H), 2.80 (m, 2H), 3.02 (s, 3H),
3.54 (q, 2H), 3.81 (s, 3H), 7.01 (s, 1H), 7.37 (s, 1H), 7.67 (brs,
2H), 7.87 (t, 1H). Example 160 ##STR00206## N-[4-(8- methoxy-1,6-
dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)-
butyl]-3- methyl- butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45 (m, 2H), 1.66 (m,
2H), 1.85 (d, 2H), 1.85 (m. 1H), 2.58 (s, 3H), 3.02 (s, 2H), 3.04
(q, 2H), 3.38 (s, 3H), 7.00 (s, 1H), 7.37 (s, 1H), 7.68 (t, 1H),
7.80 (t, 1H). Example 161 ##STR00207## [4-(8- methoxy-1,6-
dimethyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]-
carbamic acid isopropylester Mass (M + H.sup.+): 399.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45 (m, 2H), 1.66 (m,
2H), 1.85 (d, 2H), 1.85 (m. 1H), 2.58 (s, 3H), 3.02 (s, 2H), 3.04
(q, 2H), 3.38 (s, 3H), 7.00 (s, 1H), 7.37 (s, 1H), 7.68 (t, 1H),
7.80 (t, 1H).
<Preparative Example 13> Preparation of
4-chloro-7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline
##STR00208##
[1125]
4-Chloro-7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline was obtained by the same manner as described in
Preparative Example 5, except that
6,7-bis-(2-methoxy-ethoxy)-1,4-dihydro-quinoxaline-2,3-dione was
used.
Step 1: Preparation of
2,3-dichloro-6,7-bis-(2-methoxy-ethoxy)-quinoxaline
[1126] Mass (M+H.sup.+): 347.0
[1127] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.31 (s, 6H), 3.72
(t, 4H), 4.29 (t, 4H), 7.45 (s, 2H).
Step 2: Preparation of
[3-chloro-6,7-bis-(2-methoxy-ethoxy)-quinoxaline-2-yl]-hydrazine
[1128] Mass (M+H.sup.+): 343.1
[1129] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.30 (s, 6H), 3.68
(m, 4H), 4.15 (t, 2H), 4.20 (t, 2H), 4.43 (brs, 2H), 7.08 (s, 1H),
7.19 (s, 1H), 8.36 (s, 1H).
Step 3: Preparation of
4-chloro-7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline
[1130] Mass (M+H.sup.+): 367.1
[1131] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.07 (s, 3H), 3.30
(s, 3H), 3.32 (s, 3H), 3.69 (t, 2H), 3.74 (t, 2H), 4.24 (t, 2H),
4.38 (t, 2H), 7.56 (s, 1H), 7.75 (s, 1H).
<Example 162> Preparation of
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00209##
[1133] 1.14 g of a target compound was obtained (70% yield) by the
same manner as described in Example 57, except that
4-chloro-7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline (1.15 g, 3.14 mmol) prepared in step 3 of Preparative Example
13 was used.
[1134] Mass (M+H.sup.+): 519.3
[1135] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43
(m, 2H), 1.59 (m, 2H), 2.91 (m, 2H), 3.00 (s, 3H), 3.27 (s, 3H),
3.31 (s, 3H), 3.46 (m, 2H), 3.67 (m, 4H), 4.16 (m, 2H), 4.21 (m,
2H), 6.75 (t, 1H), 7.11 (s, 1H), 7.57 (s, 1H), 7.81 (t, 1H).
<Example 163> Preparation of
N.sup.1-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinox-
aline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00210##
[1137] 1.22 g of a target compound was obtained (88% yield) by the
same manner as described in Example 58, except that
{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester (1.1 g, 2.1 mmol)
prepared in Example 162 was used.
[1138] Mass (M+H.sup.+): 419.2
[1139] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.68
(m, 2H), 2.82 (m, 2H), 3.01 (s, 3H), 3.31 (s, 6H), 3.53 (q, 2H),
3.68 (m, 4H), 4.16 (t, 2H), 4.22 (t, 2H), 7.11 (s, 1H), 7.59 (s,
brm, 2H), 7.93 (t, 1H).
<Example 164> Preparation of
N-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxali-
ne-4-ylamino]-butyl}-2,2-dimethyl-propionamide
##STR00211##
[1141] 111 mg of a target compound was obtained (100% yield) by the
same manner as described in Example 59, except that
N.sup.1-{4-[7,8-bis-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qui-
noxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid (120 mg,
0.19 mmol) prepared in Example 163 was used.
[1142] Mass (M+H.sup.+): 503.3
[1143] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.02 (s, 9H), 1.45 (m,
2H), 1.60 (m, 2H), 3.00 (s, 3H), 3.04 (q, 2H), 3.30 (s, 3H), 3.31
(s, 3H), 3.47 (q, 2H), 3.67 (m, 4H), 4.16 (t, 2H), 4.22 (t, 2H),
7.11 (s, 1H), 7.37 (t, 1H), 7.58 (s, 1H), 7.81 (t, 1H).
[1144] The compounds shown in Table 12 below were prepared by the
same manner as described in Example 164.
TABLE-US-00012 TABLE 12 Example Structure Name Data Example 165
##STR00212## {4-[7,8-bis- (2-methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}- carbamic
acid isopropylester Mass (M + H.sup.+): 505.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.09 (d, 6H), 1.44 (m, 2H), 1.60 (m, 2H),
2.96 (q, 2H), 3.00 (s, 3H), 3.30 (s, 3H), 3.31 (s, 3H), 3.47 (q,
2H), 3.67 (m, 4H), 4.18 (t, 2H), 4.21 (t, 2H), 4.68 (m, 1H), 6.94
(t, 1H), 7.12 (s, 1H), 7.58 (s, 1H), 7.82 (t, 1H). Example 166
##STR00213## N-{4-[7,8- bis-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}-3- methyl-
butyramide Mass (M + H.sup.+): 503.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.80 (d, 6H), 1.44 (t, 2H), 1.61 (t, 2H), 1.86 (t,
2H), 1.91 (m, 1H), 3.00 (s, 3H), 3.04 (q, 2H), 3.30 (s, 3H), 3.33
(s, 3H), 3.48 (q, 2H), 3.67 (m, 4H), 4.16 (t, 2H), 4.22 (t, 2H),
7.11 (s, 1H), 7.58 (s, 1H), 7.89 (t, 1H), 7.82 (t, 1H). Example 167
##STR00214## N-{4-[7,8- bis-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}-3,3-
dimethyl- butyramide Mass (M + H.sup.+): 517.1; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.88 (s, 9H), 1.43 (m, 2H), 1.62 (m, 2H),
1.87 (s, 2H), 3.00 (s, 3H), 3.03 (m, 2H), 3.30 (s, 3H), 3.31 (s,
3H), 3.48 (q, 2H), 3.67 (m, 4H), 4.16 (t, 2H), 4.22 (t, 2H), 7.11
(s, 1H), 7.58 (s, 1H), 7.64 (t, 1H), 7.83 (t, 1H). Example 168
##STR00215## {4-[7,8-bis- (2-methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}- carbamic
acid isobutylester Mass (M + H.sup.+): 519.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.81 (d, 6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.76 (m,
1H), 2.97 (m, 2H), 3.00 (s, 3H), 3.48 (q, 2H), 3.67 (m, 6H), 4.17
(t, 2H), 4.22 (t, 2H), 7.03 (t, 1H), 7.12 (s, 1H), 7.58 (s, 1H),
7.82 (t, 1H). Example 169 ##STR00216## 1-{4-[7,8- bis-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]-
butyl}-3- tert-butyl- urea Mass (M + H.sup.+): 518.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.15 (s, 9H), 1.39 (m, 2H), 1.60 (m,
2H), 2.93 (q, 2H), 3.00 (s, 3H), 3.30 (s, 3H), 3.31 (s, 3H), 3.48
(q, 2H), 3.67 (m, 4H), 4.17 (t, 2H), 4.22 (t, 2H), 5.49 (s, 1H),
5.57 (t, 1H), 7.12 (s, 1H), 7.58 (s, 1H), 7.83 (t, 1H). Example 170
##STR00217## N-{4-[7,8- bis-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}- benzamide
Mass (M + H.sup.+): 523.3; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.59 (m, 2H), 1.67 (m, 2H), 3.00 (s, 3H), 3.27 (s, 3H), 3.29
(s, 3H), 3.51 (m, 2H), 3.67 (m, 4H), 4.14 (t, 2H), 4.21 (t, 2H),
7.11 (s, 1H), 7.39 (dd, 2H), 7.46 (m, 1H), 7.58 (s, 1H), 7.78 (d,
2H), 7.85 (t, 1H), 8.04 (t, 1H). Example 171 ##STR00218##
N-{4-[7,8- bis-(2- methoxy- ethoxy)-1- methyl- [1,2,4]triazolo
[4,3-a] quinoxaline-4- ylamino]- butyl}-2- chloro- benzamide Mass
(M + H.sup.+): 557.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.56
(m, 2H), 1.71 (m, 2H), 3.01 (s, 3H), 3.23 (q, 2H), 3.29 (s, 3H),
3.31 (s, 3H), 3.52 (q, 2H), 3.68 (m, 4H), 4.15 (t, 2H), 4.22 (t,
2H), 7.12 (s, 1H), 7.20 (m, 1H), 7.33 (t, 1H), 7.36 (t, 1H), 7.42
(d, 1H), 7.58 (s, 1H), 7.85 (t, 1H), 8 .36 (t, 1H). Example 172
##STR00219## N-{4-[7,8- bis-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}-2-
chloro-6- methyl- nicotinamide Mass (M + H.sup.+): 572.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.57 (m, 2H), 1.71 (m, 2H), 2.41 (s,
3H), 3.01 (s, 3H), 3.22 (q, 2H), 3.30 (s, 3H), 3.31 (s, 3H), 3.49
(q, 2H), 3.68 (m, 4H), 4.15 (t, 2H), 4.22 (t, 2H), 7.12 (s, 1H),
7.24 (d, 1H), 7.58 (s, 1H), 7.68 (d, 1H), 7.86 (t, 1H), 8.44 (t,
1H).
<Preparative Example 14> Preparation of
4-chloro-7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00220##
[1146]
4-Chloro-7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
was obtained by the same manner as described in Preparative Example
5, except that 6,7-diethoxy-1,4-dihydro-quinoxaline-2,3-dione was
used.
Step 1: Preparation of 2,3-dichloro-6,7-diethoxy-quinoxaline
[1147] Mass (M+H.sup.+): 288.0
Step 2: Preparation of
(3-chloro-6,7-diethoxy-quinoxaline-2-yl)-hydrazine
[1148] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.36 (m, 6H), 4.08 (m,
4H), 4.40 (brm, 2H), 6.93 (s, 1H), 7.64 (s, 1H), 8.31 (s, 1H).
Step 3: Preparation of
4-chloro-7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1149] Mass (M+H.sup.+): 307.2
[1150] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.40 (m, 6H), 3.05
(s, 3H), 4.24 (m, 4H), 7.50 (s, 1H), 7.65 (s, 1H).
[1151] The compounds shown in Table 13 below were prepared by using
4-chloro-7,8-diethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared by the same manner as described in Preparative Example 14
as an intermediate.
TABLE-US-00013 TABLE 13 Example Structure Name Data Example 173
##STR00221## [4-(7,8- diethoxy-1- methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl- carbamic acid-tert- butylester Mass
(M + H.sup.+): 459.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32
(s, 9H), 1.34 (m, 6H), 1.42 (m, 2H), 1.65 (m, 2H), 2.92 (q. 2H),
3.00 (s, 1H), 3.46 (q, 2H), 4.12 (m, 4H), 6.75 (t, 1H), 7.08 (s,
1H), 7.50 (s, 1H), 7.79 (t, 1H). Example 174 ##STR00222##
N.sup.1-(7,8- diethoxy-1- methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4-yl)- butane-1,4- diamine ditrifluoroacetic acid Mass
(M + H.sup.+): 359.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.34
(m, 6H), 1.59 (m, 2H), 1.68 (m, 2H), 2.81 (q, 2H), 3.01 (s. 3H),
3.51 (q, 2H), 4.09 (m, 2H), 4.14 (m, 2H), 7.09 (s, 1H), 7.51 (s,
1H), 7.67 (brs, 2H), 8.08 (brs, 1H). Example 175 ##STR00223##
[4-(7,8- diethoxy-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline-4-
ylamino)- butyl]- carbamic acid isopropylester Mass (M + H.sup.+):
445.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.10 (d, 6H), 1.16
(m, 6H), 1.36 (m, 2H), 1.60 (m, 2H), 3.00 (q. 2H), 3.05 (s, 3H),
3.47 (q, 2H), 4.12 (m, 4H), 4.68 (m, 1H), 6.94 (t, 1H), 7.09 (s,
1H), 7.50 (s, 1H), 7.80 (t, 1H). Example 176 ##STR00224## [4-(7,8-
diethoxy-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline-4-
ylamino)- butyl]- carbamic acid isobutylester Mass (M + H.sup.+):
459.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.82 (d, 6H), 1.13
(d, 2H), 1.32 (m, 6H), 1.44 (m, 2H), 1.61 (m. 2H), 1.76 (m, 1H),
3.00 (s, 3H), 3.47 (q, 2H), 3.66 (q, 2H), 4.12 (m, 4H), 7.03 (t,
1H), 7.08 (s, 1H), 7.50 (s, 1H), 7.78 (t, 1H). Example 177
##STR00225## N-[4-(7,8- diethoxy-1- methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino)- butyl-3- methyl- butyramide Mass (M +
H.sup.+): 443.2; .sup.1H NMR (500 MHz, DMSO-d6): 0.80 (d, 6H), 1.33
(m, 6H), 1.41 (m, 2H), 1.70 (m, 2H), 1.86 (m. 1H), 1.87 (m, 2H),
3.00 (s, 3H), 3.04 (q, 2H), 3.47 (q, 2H), 4.12 (m, 4H), 7.08 (s,
1H), 7.51 (s, 1H), 7.69 (t, 1H), 7.79 (t, 1H).
<Preparative Example 15> Preparation of
4-chloro-1-methyl-8,9-dihydro-7,10-dioxy-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene
##STR00226##
[1153]
4-Chloro-1-methyl-8,9-dihydro-7,10-dioxy-2,3,5,11b-tetraaza-cyclope-
nta[a]anthracene was obtained by the same manner as described in
Preparative Example 5, except that
2,3,5,8-tetrahydro-1,4-dioxa-5,8-diaza anthracene-6,7-dione was
used.
Step 1: Preparation of
6,7-dichloro-2,3-dihydro-1,4-dioxa-5,8-diaza-anthracene
[1154] Mass (M+H.sup.+): 257.0
[1155] .sup.1H NMR (500 MHz, DMSO-d6): .delta.4.41 (s, 4H), 7.45
(s, 2H).
Step 2: Preparation of
(7-dichloro-2,3-dihydro-1,4-dioxa-5,8-diaza-anthracene-6-yl)-hydrazine
[1156] Mass (M+H.sup.+): 253.0
Step 3: Preparation of
4-chloro-1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene
[1157] Mass (M+H.sup.+): 277.0
[1158] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.02 (s, 3H), 4.36 (t,
2H), 4.39 (t, 2H), 7.49 (s, 1H), 7.70 (s, 1H).
<Example 178> Preparation of
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid-tert-butylester
##STR00227##
[1160] 2 g of a target compound was obtained (82% yield) by the
same manner as described in Example 57, except that
4-chloro-1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene (1.58 g, 5.71 mmol) prepared in step 3 of Preparative
Example 15 was used.
[1161] Mass (M+H.sup.+): 429.2
[1162] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.41
(m, 2H), 1.58 (m, 2H), 2.90 (m, 2H), 2.92 (s, 3H), 3.44 (q, 2H),
4.27 (s, 4H), 6.74 (t, 1H), 7.01 (s, 1H), 7.47 (s, 1H), 7.82 (t,
1H).
<Example 179> Preparation of
N.sup.1-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene-4-yl)-butane-1,4-diamine ditrifluoroacetic acid
##STR00228##
[1164] 2.2 g of a target compound was obtained (89% yield) by the
same manner as described in Example 58, except that
[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]anthr-
acene-4-ylamino)-butyl]-carbamic acid-tert-butylester (1.9 g, 4.43
mmol) prepared in Example 178 was used.
[1165] Mass (M+H.sup.+): 329.2
[1166] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.58 (m, 2H), 1.66
(m, 2H), 2.82 (m, 2H), 2.94 (s, 3H), 3.48 (q, 2H), 4.28 (s, 4H),
7.01 (s, 1H), 7.49 (s, 1H), 7.60 (brs, 2H), 7.94 (brm, 1H).
<Example 180> Preparation of
2,2-dimethyl-N-[4-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyc-
lopenta[a]anthracene-4-ylamino)-butyl]-propionamide
##STR00229##
[1168] 52 mg of a target compound was obtained (60% yield) by the
same manner as described in Example 59, except that
N.sup.1-(1-methyl-8,9-dihydro-7,10-dioxa-2,3,5,11b-tetraaza-cyclopenta[a]-
anthracene-4-yl)-butane-1,4-diamine ditrifluoroacetic acid (120 mg,
0.22 mmol) prepared in Example 179 was used.
[1169] Mass (M+H.sup.+): 413.2
[1170] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.43
(m, 2H), 1.58 (m, 2H), 2.93 (s, 3H), 3.03 (q, 2H), 3.44 (q, 2H),
4.27 (s, 4H), 6.99 (s, 1H), 7.36 (t, 1H), 7.47 (s, 1H), 7.81 (t,
1H).
[1171] The compounds shown in Table 14 below were prepared by the
same manner as described in Example 180.
TABLE-US-00014 TABLE 14 Example Structure Name Data Example 181
##STR00230## 3-methyl-N- [4-(1- methyl-8,9- dihydro- 7,10-dioxa-
2,3,5,11b- tetraaza- cyclopenta[a] anthracene- 4-ylamino)- butyl]-
butyramide Mass (M + H.sup.+): 413.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 1.42 (m, 2H), 1.60 (m, 2H), 1.87 (d,
2H), 1.89 (m, 1H), 2.93 (s, 3H), 3.02 (q, 2H), 3.45 (q, 2H), 4.27
(s, 4H), 7.00 (s, 1H), 7.47 (s, 1H), 7.68 (t, 1H), 7.82 (t, 1H).
Example 182 ##STR00231## 2-(R)- hydroxy-3- methyl-N-[4- (1-methyl-
8,9-dihydro- 7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a]
anthracene- 4-ylamino)- butyl]- butyramide Mass (M + H.sup.+):
429.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.82
(d, 3H), 1.46 (m, 2H), 1.59 (m, 2H), 1.91 (m, 1H), 2.92 (s, 3H),
3.05 (m, 1H), 3.11 (m, 1H), 3.44 (q, 2H), 3.60 (t, 1H), 4.27 (s,
4H), 5.23 (d, 1H), 6.99 (s, 1H), 7.46 (m, 1H), 7.65 (t, 1H), 7.82
(t, 1H). Example 183 ##STR00232## 2-(S)- hydroxy-3- methyl-N-[4-
(1-methyl- 8,9-dihydro- 7,10-dioxa- 2,3,5,11b- tetraaza-
cyclopenta[a] anthracene- 4-ylamino)- butyl]- butyramide Mass (M +
H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d,
3H), 0.83 (d, 3H), 1.45 (m, 2H), 1.59 (m, 2H), 1.91 (m, 1H), 2.92
(s, 3H), 3.05 (m, 1H), 3.12 (m, 1H), 3.45 (q, 2H), 3.59 (t, 1H),
4.27 (s, 4H), 5.22 (d, 1H), 6.99 (s, 1H), 7.47 (m, 1H), 7.64 (t,
1H), 7.82 (t, 1H). Example 184 ##STR00233## acetic acid- [4-(1-
methyl-8,9- dihydro- 7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a]
anthracene- 4-ylamino)- butyl]- carbamoyl]- methylester Mass (M +
H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.45 (m,
2H), 1.59 (m, 2H), 2.03 (s, 3H), 2.93 (s, 3H), 3.08 (q, 2H), 3.45
(q, 2H), 4.27 (s, 4H), 4.36 (s, 2H), 7.00 (s, 1H), 7.47 (s, 1H),
7.80 (t, 1H), 7.93 (t, 1H). Example 185 ##STR00234## N-[4-(1-
methyl-8,9- dihydro- 7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a]
anthracene- 4-ylamino)- butyl]-2- thiophene-2- yl-acetamide Mass (M
+ H.sup.+): 453.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.46 (m,
2H), 1.61 (m, 2H), 2.923 (s, 3H), 3.06 (q, 2H), 3.46 (q, 2H), 3.56
(s, 2H), 4.27 (s, 4H), 6.83 (d, 1H), 6.87 (q, 1H), 7.01 (s, 1H),
7.26 (d, 1H), 7.48 (s, 1H), 7.83 (t, 1H), 8.01 (t, 1H). Example 186
##STR00235## N-[4-(1- methyl-8,9- dihydro- 7,10-dioxa- 2,3,5,11b-
tetraaza- cyclopenta[a] anthracene- 4-ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 433.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.57 (m, 2H), 1.67 (m, 2H), 2.92 (s, 3H), 3.27 (m, 2H), 3.49
(q, 2H), 4.27 (s, 4H), 7.00 (s, 1H), 7.39 (t, 2H), 7.45 (t, 1H),
7.47 (s, 1H), 7.77 (dd, 2H), 7.83 (t, 1H), 8.39 (t, 1H). Example
187 ##STR00236## 2-chloro-N- [4-(1- methyl-8,9- dihydro-
7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a] anthracene-
4-ylamino)- butyl]- benzamide Mass (M + H.sup.+): 467.1; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.55 (m, 2H), 1.70 (m, 2H), 2.93 (s,
3H), 3.22 (q, 2H), 3.48 (q, 2H), 7.01 (s, 1H), 7.30 (t, 1H), 7.33
(m, 1H), 7.38 (t, 1H), 7.42 (d, 1H), 7.48 (s, 1H), 7.85 (t, 1H),
8.35 (t, 1H). Example 188 ##STR00237## [4-(1- methyl-8,9- dihydro-
7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a] anthracene-
4-ylamino)- butyl]- carbamic acid isopropylester Mass (M +
H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.09 (d,
6H), 1.42 (m, 2H), 1.59 (m, 2H), 2.93 (s, 3H), 2.96 (q, 2H), 3.45
(q, 2H), 4.27 (s, 4H), 4.68 (m, 1H), 6.93 (t, 1H), 7.01 (s, 1H),
7.47 (s, 1H), 7.81 (t, 1H). Example 189 ##STR00238## [4-(1-
methyl-8,9- dihydro- 7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a]
anthracene- 4-ylamino)- butyl]- carbamic acid isobutylester Mass (M
+ H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81 (d,
6H), 1.43 (m, 2H), 1.59 (m, 2H), 1.76 (m, 1H), 2.93 (s, 3H), 2.97
(q, 2H), 3.66 (d, 2H), 4.27 (s, 4H), 7.00 (s, 1H), 7.03 (t, 1H),
8.83 (t, 1H). Example 190 ##STR00239## [4-(1- methyl-8,9- dihydro-
7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a] anthracene-
4-ylamino)- butyl]- carbamic acid cyclopentylester Mass (M +
H.sup.+): 441.2; .sup.1H NMR (500 MHz, DMSO-d6): 1.38~1.60 (m,
10H), 1.73 (m, 2H), 2.93 (s, 3H), 2.96 (m, 2H), 3.45 (q, 2H), 4.27
(s, 4H), 4.88 (m, 1H), 6.93 (t, 1H), 7.01 (s, 1H), 7.47 (s, 1H),
7.81 (t, 1H). Example 191 ##STR00240## [4-(1- methyl-8,9- dihydro-
7,10-dioxa- 2,3,5,11b- tetraaza- cyclopenta[a] anthracene-
4-ylamino)- butyl]- carbamic acid phenylester Mass (M + H.sup.+):
449.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.52 (m, 2H), 1.66
(m, 2H), 2.93 (s, 3H), 3.07 (q, 2H), 3.48 (m, 2H), 4.27 (s, 4H),
7.02 (s, 2H), 7.04 (m, 1H), 7.14 (t, 1H), 7.32 (t, 2H), 7.49 (s,
1H), 7.70 (t, 1H), 7.88 (t, 1H). Example 192 ##STR00241##
1-isopropyl- 3-[4-(1- methyl-8,9- dihydro- 7,10-dioxa- 2,3,5,11b-
tetraaza- cyclopenta[a] anthracene- 4-ylamino)- butyl]-urea Mass (M
+ H.sup.+): 414.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.95 (d,
6H), 1.39 (m, 2H), 1.58 (m, 2H), 2.93 (s, 3H), 2.97 (q, 2H), 3.45
(q, 2H), 3.59 (m, 1H), 4.27 (s, 4H), 5.52 (d, 1H), 5.61 (t, 1H),
7.01 (s, 1H), 7.47 (s, 1H), 7.82 (t, 1H).
<Preparative Example 16> Preparation of
4-chloro-6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00242##
[1173]
4-Chloro-6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e was obtained by the same manner as described in Preparative
Example 5 was used.
Step 1: Preparation of 2,3-chloro-5,6,7-trimethoxy-quinoxaline
[1174] Mass (M+H.sup.+): 289.0
[1175] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.91 (s, 3H), 3.96
(s, 3H), 4.01 (s, 3H), 7.31 (s, 1H).
Step 2: Preparation of
[3-chloro-5,6,7-trimethoxy)-quinoxaline-2-yl]hydrazine
[1176] Mass (M+H.sup.+): 283.1
Step 3: Preparation of
4-chloro-6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
[1177] Mass (M+H.sup.+): 309.0
[1178] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.13 (s, 3H), 3.78 (s,
3H), 3.99 (s, 3H), 4.03 (s, 3H), 7.49 (s, 1H)
<Example 193> Preparation of
[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester
##STR00243##
[1180] 0.35 g of a target compound was obtained (61% yield) by the
same manner as described in Example 57, except that
4-chloro-1-methyl-6,7,8-trimethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
prepared in step 3 of Preparative Example 16 was used.
[1181] Mass (M+H.sup.+): 461.2
[1182] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43
(m, 2H), 1.62 (m, 2H), 2.92 (m, 2H), 3.03 (s, 3H), 3.50 (q, 2H),
3.76 (s, 3H), 3.89 (s, 3H), 3.97 (s, 3H), 6.73 (t, 1H), 7.35 (s,
1H), 7.93 (t, 1H).
<Example 194> Preparation of
N.sup.1-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid
##STR00244##
[1184] 0.29 g of a target compound was obtained (67% yield) by the
same manner as described in Example 58, except that
[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester prepared in Example 193 was
used.
[1185] Mass (M+H.sup.+): 361.2
<Example 195> Preparation of
3-methyl-N-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide
##STR00245##
[1187] 0.06 g of a target compound was obtained (51% yield) by the
same manner as described in Example 37, except that
N.sup.1-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid prepared in Example 194
was used.
[1188] Mass (M+H.sup.+): 445.1
[1189] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45
(m, 2H), 1.63 (m, 2H), 1.85 (m, 2H), 1.87 (m, 1H), 3.03 (q, 2H),
3.04 (s, 3H), 3.51 (m, 2H), 3.76 (s, 3H), 3.89 (s, 3H), 3.96 (s,
3H), 7.36 (s, 1H), 7.68 (t, 1H), 7.94 (t, 1H)
<Example 196> Preparation of 3-methyl-pentanoic
acid-[4-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide
##STR00246##
[1191] 0.03 g of a target compound was obtained (30% yield) by the
same manner as described in Example 73, except that
N.sup.1-(6,7,8-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid prepared in Example 194
was used.
[1192] Mass (M+H.sup.+): 459.2
[1193] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 6H),
1.06-1.23 (brm, 2H), 1.44 (m, 2H), 1.63 (m, 2H), 1.78 (m, 2H), 1.97
(m, 1H), 3.04 (q, 2H), 3.05 (s, 3H), 3.50 (q, 2H), 3.77 (s, 3H),
3.89 (s, 3H), 3.95 (s, 3H), 7.36 (s, 1H), 7.68 (t, 1H), 7.94 (t,
1H).
<Preparative Example 17> Preparation of
methyl-3-chloro-2-hydrazinylquinoxaline-6-carboxylate
##STR00247##
[1194] Step 1: Preparation of
methyl-2,3-dichloroquinoxaline-6-carboxylate
[1195] A target compound was obtained (72% yield) by the same
manner as described in step 1 of Preparative Example 5, except that
methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylate (7 g,
31.8 mmol) was used.
[1196] Mass (M+H.sup.+): 257.1
[1197] .sup.1H NMR (300 MHz, DMSO-d6): .delta.3.96 (s, 3H), 7.12
(d, J=8.65 Hz, 1H), 7.28 (d, J=8.65 Hz, 1H), 8.45 (s, 1H).
Step 2: Preparation of
methyl-3-chloro-2-hydrazinylquinoxaline-6-carboxylate
[1198] A target compound was obtained (91% yield) by the same
manner as described in step 2 of Preparative Example 5, except that
methyl-2,3-dichloroquinoxaline-6-carboxylate (5.42 g, 21.1 mmol)
prepared in step 1 of Preparative Example 17 was used.
[1199] Mass (M+H.sup.+): 253.0
Step 3: Preparation of
methyl-4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylate
[1200] A target compound was obtained (86% yield) by the same
manner as described in step 3 of Preparative Example 5, except that
methyl-3-chloro-2-hydrazinylquinoxaline-6-carboxylate (5.50 g, 21.8
mmol) prepared in step 2 of Preparative Example 17 was used.
[1201] Mass (M+H.sup.+): 277.0
[1202] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.13 (s, 3H), 3.95 (s,
3H), 8.27 (dd, J=8.75, 1.50 Hz, 1H), 7.48 (d, J=8.75 Hz, 1H), 8.45
(d, J=1.50 Hz, 1H).
<Example 197> Preparation of
4-(4-tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-7-carboxylic acid methylester
##STR00248##
[1204] A target compound was obtained (79% yield) by the same
manner as described in Example 57, except that
methyl-4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylate
(2 g, 7.23 mmol) prepared in step 3 of Preparative Example 16 was
used.
[1205] Mass (M+H.sup.+): 429.2
[1206] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.44-1.50 (m, 2H),
1.64-1.70 (m, 2H), 2.95-2.99 (m, 2H), 3.04 (s, 3H), 3.53-3.57 (m,
2H), 3.91 (s, 3H), 6.81 (t, J=5.40 Hz, 1H), 8.10 (d, J=1.95 Hz,
1H), 8.20 (d, J=8.70 Hz, 1H), 8.37 (t, J=5.70 Hz, 1H), 8.82 (dd,
J=8.70 Hz, 1.95 Hz, 1H).
<Example 198> Preparation of
4-(4-amino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carbo-
xylic acid methylester ditrifluoroacetic acid
##STR00249##
[1208] 2 g of a target compound was obtained (77% yield) by the
same manner as described in Example 58, except that
4-(4-tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a-
]quinoxaline-7-carboxylic acid methylester (2 g, 4.67 mmol)
prepared in Example 197 was used.
[1209] Mass (M+H.sup.+): 329.1
[1210] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.60 (m, 2H), 1.70
(m, 2H), 2.81 (m, 2H), 3.01 (s, 3H), 3.56 (m, 2H), 3.87 (s, 3H),
7.61 (brs, 1H), 7.81 (d, 1H). 8.08 (s, 1H), 8.19 (d, 1H), 8.39 (t,
1H).
<Example 199> Preparation of
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid methylester
##STR00250##
[1212] 0.71 g of a target compound was obtained (95% yield) by the
same manner as described in Example 37, except that
4-(4-amino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-7-carbo-
xylic acid methylester ditrifluoroacetic acid (1 g, 1.8 mmol)
prepared in Example 198 was used.
[1213] Mass (M+H.sup.+): 413.2
[1214] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.78 (d, 6H), 1.45 (m,
2H), 1.63 (m, 2H), 1.86 (d, 2H), 1.88 (m, 1H), 2.99 (s, 3H), 3.05
(q, 2H), 3.51 (q, 2H), 3.86 (s, 3H), 7.69 (t, 1H), 7.78 (d, 1H),
8.05 (s, 1H), 8.15 (d, 1H), 8.31 (t, 1H).
<Example 200> Preparation of
4-[(4-tert-butoxycarbamoylamino)-butylamino]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-7-carboxylic acid
##STR00251##
[1216]
4-(4-tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-7-carboxylic acid methylester (2 g, 4.67 mmol)
prepared in Example 197 was dissolved in tetrahydrofuran, to which
water containing sodium hydroxide (0.56 g, 14 mmol) dissolved
therein was added dropwise, followed by stirring at room
temperature for 17 hours. Upon completion of the reaction,
tetrahydrofuran solvent was eliminated by distillation under reduce
pressure, and pH was adjusted to 2-3 with 1 N hydrochloric acid
aqueous solution. The resulting solid was filtered and vacuum
dried. As a result, a target compound was obtained (86% yield).
[1217] Mass (M+H.sup.+): 415.2
[1218] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.35 (s, 9H),
1.45-1.49 (m, 2H), 1.65-1.67 (m, 2H), 2.96-2.98 (m, 2H), 3.04 (s,
3H), 3.57-3.58 (m, 2H), 6.80 (s, 1H), 8.83 (d, J=8.52 Hz, 1H), 8.15
(s, 1H), 8.20 (d, J=8.70 Hz, 1H), 8.51 (brs, 1H), 13.14 (brs,
1H).
<Example 201> Preparation of
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid
##STR00252##
[1220] 3.9 g of a target compound was obtained (100% yield) by the
same manner as described in Example 200, except that
1-methyl-4-[4-(3-methyl-butyrylamino)-butylamino]-[1,2,4]triazolo[4,3-a]q-
uinoxaline-7-carboxylic acid methylester (4 g, 9.7 mmol) prepared
in Example 199 was used.
[1221] Mass (M+H.sup.+): 399.2
[1222] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.78 (d, 6H), 1.46 (m,
2H), 1.64 (m, 2H), 1.86 (s, 2H), 1.88 (m, 1H), 3.00 (s, 3H), 3.04
(q, 2H), 3.52 (m, 2H), 7.68 (t, 1H), 7.78 (d, 1H), 8.04 (s, 1H),
8.14 (d, 1H), 8.28 (t, 1H), 13.05 (s, 1H)
<Example 202>[Preparation of
4-(7-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-carbamic acid-tert-butylester
##STR00253##
[1224]
4-(4-Tert-butoxycarbamoylamino-butylamino)-1-methyl-[1,2,4]triazolo-
[4,3-a]quinoxaline-7-carboxylic acid (0.50 g, 1.21 mmol) prepared
in Example 200, isopropylamine (0.09 g, 1.45 mmol), HCTU (0.60 g,
1.45 mmol) and diisopropylethylamine (0.85 mL, 4.84 mmol) were
dissolved in dimethylformamide, followed by stirring at room
temperature for 2 hours. Upon completion of the reaction, the
reactant was extracted with ethylacetate and sodium bicarbonate
solutions 3 times, followed by washing the organic layer with
sodium bicarbonate solution. The organic layer was dried over
magnesium sulfate, filtered, distilled under reduced pressure, and
purified by MPLC. As a result, a target compound was obtained (82%
yield).
[1225] Mass (M+H.sup.+): 455.8
[1226] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.19 (d, J=6.30 Hz,
6H), 1.36 (s, 9H), 1.42-1.49 (m, 2H), 1.64-1.69 (m, 2H), 2.95-2.97
(m, 2H), 3.04 (s, 3H), 3.54-3.56 (m, 2H), 4.08-4.17 (m, 1H), 6.80
(brs, 1H), 7.76 (d, J=8.55 Hz, 1H), 8.12-8.15 (m, 2H), 8.26 (brs,
1H), 8.43 (d, J=7.38 Hz, 1H).
[1227] The compounds shown in Table 15 below were prepared by the
same manners as described in Example 197 Example
TABLE-US-00015 TABLE 15 Example Structure Name Data Example 203
##STR00254## [4-(7-tert-- butylcarbamoyl- 1-methyl- [1,2,4]triazolo
[4,3-a] quinoxaline-4- ylamino)- butyl]- carbamic acid-tert-
butylester Mass (M + H.sup.+): 469.5; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.36 (s, 9H), 1.41 (s, 9H), 1.43-1.49 (m, 2H),
1.65-1.71 (m, 2H), 2.92-2.99 (m, 2H), 3.04 (s, 3H), 3.54- 3.56 (m,
2H), 6.80 (brs, 1H), 7.71 (d, J = 8.49 Hz, 1H), 8.06 (s, 1H), 8.11
(d, J = 8.49 Hz, 1H), 8.23 (brs, 1H). Example 204 ##STR00255##
4-(4- isobutylamino- butylamino)- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-7- carboxylic acid isopropylamide Mass (M + H.sup.+):
426.3; .sup.1H NMR (300 MHz, DMSO-d6): .delta.0.97 (d, J = 6.81 Hz,
6H), 1.19 (d, J = 6.60 Hz, 6H), 1.44-1.53 (m, 2H), 1.63-1.73 (m,
2H), 2.27-2.36 (m, 1H), 3.04 (s, 3H), 3.05-3.11 (m, 2H), 3.53-3.59
(m, 2H), 4.09-4.20 (m, 1H), 7.68 (t, J = 5.28 Hz, 1H), 7.77 (dd, J
= 8.64 Hz, 1.95 Hz, 1H), 8.12- 8.16 (m, 2H), 8.30 (brs, 1H), 8.44
(d, J = 7.77 Hz, 1H). Example 205 ##STR00256## 4-(4- benzoylamino-
butylamino)- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-7-
carboxylic acid isopropylamide Mass (M + H.sup.+): 460.2; .sup.1H
NMR (300 MHz, DMSO-d6): .delta.1.19 (d, J = 6.57 Hz, 6H), 1.59-1.68
(m, 2H), 1.71-1.79 (m, 2H), 3.04 (s, 3H), 3.28- 3.34 (m, 2H), 3.57-
3.62 (m, 2H), 4.06- 4.18 (m, 1H), 7.40- 7.50 (m, 3H), 7.75- 7.83
(m, 3H), 8.13- 8.16 (m, 2H), 8.27 (t, J = 5.79 Hz, 1H), 8.42-8.47
(m, 2H). Example 206 ##STR00257## {4-[7-(2- dimethylamino-
ethylcarbamoyl)- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-4-
ylamino]- butyl}- carbamic acid-tert- butylester Mass (M +
H.sup.+): 385.3; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s,
9H), 1.40-1.52 (m, 2H), 1.62-1.69 (m, 2H), 2.90 (s, 6H), 2.93-3.00
(m, 2H), 3.05 (s, 3H), 3.18- 3.22 (m, 2H), 3.52- 3.64 (m, 4H), 6.81
(brs, 1H), 7.77 (dd, J = 8.64 Hz, 1.89 Hz, 1H), 8.14 (d, J = 1.77
Hz, 1H), 8.18 (d, J = 8.70 Hz, 1H), 8.31 (t, J = 5.67 Hz, 1H), 8.80
(t, J = 5.40 Hz, 1H). Example 207 ##STR00258## 4-(4- benzoylamino-
butylamino)- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-7-
carboxylic acid-(2- dimethylamino- ethyl)- amide Mass (M +
H.sup.+): 488.6 Example 208 ##STR00259## N-{4-[7-(4- benzyl-
piperazine- 1-carbonyl)- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino]- butyl}- benzamide Mass (M + H.sup.+):
576.5; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.60- 1.64 (m, 2H),
1.66- 1.72 (m, 2H), 3.05 (s, 3H), 3.14-3.18 (m, 3H), 3.20-3.35 (m,
4H), 3.55-3.65 (m, 6H), 4.34 (brs, 2H), 7.40-7.44 (m, 6H),
7.46-7.55 (m, 2H), 7.66-7.74 (m, 3H), 7.82-7.85 (m, 2H), 8.07 (d, J
= 1.23 Hz, 1H), 8.53- 8.56 (m, 1H). Example 209 ##STR00260## N-{4-
[1- methyl-7- (piperazine- 1-carbonyl)- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino]- butyl}- benzamide Mass (M + H.sup.+):
486.7 Example 210 ##STR00261## [4-(7- benzylcarbamoyl- 1-methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 503.7; .sup.1H NMR (300
MHz, DMSO-d6): .delta.1.35 (s, 9H), 1.41-1.52 (m, 2H), 1.64-1.72
(m, 2H), 2.92-3.00 (m, 2H), 3.04 (s, 3H), 3.52-3.59 (m, 2H), 4.50
(d, J = 5.34 Hz, 2H), 6.80 (brs, 1H), 7.24-7.82 (m, 5H), 8.17 (brs,
2H), 8.27 (brs, 1H), 9.25 (t, J = 5.85 Hz, 1H). Example 211
##STR00262## {4-[7-(4- chloro- benzylcarbamoyl)- 1-methyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino]- butyl}- carbamic
acid-tert- butylester Mass (M + H.sup.+): 537.8; .sup.1H NMR (300
MHz, DMSO-d6): .delta.1.35 (s, 9H), 1.40-1.48 (m, 2H), 1.60-1.72
(m, 2H), 2.92-3.00 (m, 2H), 3.04 (s, 3H), 3.49-3.57 (m, 2H), 4.48
(d, J = 5.40 Hz, 2H), 6.80 (brs, 1H), 7.35-7.42 (m, 5H), 7.79 (d, J
= 8.46 Hz, 1H), 8.16- 8.18 (m, 2H), 8.29 (brs, 1H), 9.27 (brs, 1H).
Example 212 ##STR00263## [4-(1- methyl-7- phenylcarbamoyl-
[1,2,4]triazolo [4,3-a] quinoxaline-4- ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 489.8; .sup.1H NMR (300
MHz, DMSO-d6): .delta.1.35 (s, 9H), 1.45-1.50 (m, 2H), 1.66-1.71
(m, 2H), 2.92-3.00 (m, 2H), 3.06 (s, 3H), 3.54-3.61 (m, 2H), 6.80
(brs, 1H), 6.81 (brs, 1H), 7.12 (t, J = 7.29 Hz, 1H), 7.37 (t, J =
8.10 Hz, 2H), 7.82-7.88 (m, 3H), 8.21-8.27 (m, 2H), 8.31 (t, J =
5.55 Hz, 1H). Example 213 ##STR00264## {4-[7-(2- amino-
phenylcarbamoyl)- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-4-
ylamino]- butyl}- carbamic acid-tert- butylester Mass (M -
H.sup.+): 503.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s,
9H), 1.44 (m, 2H), 1.64 (m, 2H), 2.92 (q, 2H), 3.02 (s, 3H), 3.53
(m, 2H), 4.90 (brs, 2H), 6.57 (t, 1H), 6.76 (d, 1H), 6.94 (t, 1H),
7.16 (d, 1H), 7.85 (d, 1H), 8.15 (m, 1H), 8.23 (s, 1H), 8.26 (m,
1H), 9.84 (s, 1H). Example 214 ##STR00265## {4-[7-(2- amino-4-
methyl- phenylcarbamoyl)- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline-4- ylamino]- butyl}- carbamic acid-tert- butylester
Mass (M + H.sup.+): 519.30; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.28 (s, 9H), 1.44 (m, 2H), 1.62 (m, 2H), 2.16 (s, 3H), 2.92
(m, 2H), 3.02 (s, 3H), 3.52 (m, 2H), 6.38 (d, 1H), 6.57 (s, 1H),
6.76 (d, 1H), 7.02 (d, 1H), 7.82 (d, 1H), 8.13 (m, 1H), 8.22 (m,
2H), 9.74 (s, 1H). Example 215 ##STR00266## 1-methyl-4- [4-(3-
methyl- butyrylamino)- butylamino]- [1,2,4]triazolo [4,3-a]
quinoxaline-7- carboxylic acid-(2- amino- phenyl)- amide Mass (M +
H.sup.+): 489.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
6H), 1.45 (m, 2H), 1.65 (m, 2H), 1.86 (s, 2H), 1.89 (m, 1H), 3.03
(s, 3H), 3.06 (m, 2H), 3.27 (brs, 2H), 3,53 (q, 2H), 6.61 (t, 1H),
6.77 (d, 1H), 6.95 (t, 1H), 7.16 (d, 1H), 7.71 (t, 1H), 7.83 (d,
1H), 8.16 (d, 1H), 8.23 (s, 1H), 8.28 (t, 1H), 9.82 (s, 1H).
Example 216 ##STR00267## 1-methyl-4- [4-(3- methyl- butyrylamino)-
butylamino]- [1,2,4]triazolo [4,3-a] quinoxaline-7- carboxylic
acid-(2- amino-4- methyl- phenyl)- amide Mass (M + H.sup.+): 503.3
Example 217 ##STR00268## 1-methyl-4- [4-(3- methyl- butyrylamino)-
butylamino]- [1,2,4]triazolo [4,3-a] quinoxaline-7- carboxylic
acid-(2- amino-4,5- dimethoxy- phenyl)- amide Mass (M + H.sup.+):
549.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta. 0.79 (d, dH), 1.46
(m, 2H), 1.65 (m, 2H), 1.87 (d, 2H), 1.91 (m, 1H), 3.02 (s, 3H),
3.05 (q, 2H), 3.54 (q, 2H), 3.61 (s, 3H), 3.68 (s, 3H), 4.54 (s,
2H), 6.45 (s, 1H), 6.81 (s, 1H), 7.70 (t, 1H), 7.83 (dd, 1H), 8.15
(d, 1H), 8.22 (s, 1H), 8.28 (t, 1H), 9.76 (s, 1H).
<Example 218> Preparation of
{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-
-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00269##
[1229]
{4-[7-(2-Amino-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester (0.70 g,
1.39 mmol) prepared in Example 213 was dissolved in 5 ml of acetic
acid, followed by stirring at 50.degree. C. for 4 hours. Upon
completion of the reaction, 5 ml of methanol was added thereto at
room temperature. Distilled water was slowly added thereto dropwise
to solidify the product. The resulting solid was filtered, washed
with water, and dried under reduced pressure. As a result, 0.54 g
of a target compound was obtained (80% yield).
[1230] Mass (M+H.sup.+): 487.3
[1231] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.45
(m, 2H), 1.64 (m, 2H), 2.95 (q, 2H), 3.04 (s, 3H), 3.55 (q, 2H)
6.78 (t, 1H), 7.20 (m, 2H), 7.58 (m, 2H), 8.08 (d, 1H), 8.21 (d,
1H), 8.29 (t, 1H), 8.38 (s, 1H).
<Example 219> Preparation of
{4-[1-methyl-7-(5-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00270##
[1233] 34 mg of a target compound was obtained (33% yield) by the
same manner as described in Example 218, except that
{4-[7-(2-amino-4-methyl-phenylcarbamoyl)-1-methyl-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester (110 mg,
0.21 mmol) prepared in Example 214 was used.
[1234] Mass (M+H.sup.+): 501.1
[1235] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.45
(m, 2H), 1.65 (m, 2H), 2.40 (s, 3H), 2.93 (q, 2H), 3.03 (s, 3H),
3.53 (q, 2H), 6.78 (t, 1H), 7.00 (d, 1H), 7.34 (brm, 1H) 7.47 (brm,
1H), 8.07 (d, 1H), 8.19 (d, 1H), 8.24 (t, 1H), 8.34 (s, 1H), 12.86
(brs, 1H).
<Example 220> Preparation of
{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00271##
[1237]
{4-[7-(1H-benzoimidazole-2-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-carbamic acid-tert-butylester (1.25 g, 2.6
mmol) prepared in Example 218 was dissolved in 15 ml of
dimethylformamide, to which potassium carbonate (0.71 g, 5.14 mmol)
was added. Iodomethane (0.19 ml, 3.1 mmol) was slowly added
thereto, followed by stirring at room temperature for 18 hours.
Upon completion of the reaction, water was slowly added thereto for
recrystallization. The resulting solid was filtered, washed with
water, and dried under reduced pressure. As a result, 1.13 g of a
target compound was obtained (85% yield).
[1238] Mass (M+H.sup.+): 487.3
[1239] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.45 (m,
2H), 1.64 (m, 2H), 2.95 (q, 2H), 3.04 (s, 3H), 3.55 (q, 2H) 6.78
(t, 1H), 7.20 (m, 2H), 7.58 (m, 2H), 8.08 (d, 1H), 8.21 (d, 1H),
8.29 (t, 1H), 8.38 (s, 1H)
<Example 221> Preparation of
N.sup.1-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00272##
[1241] 2.6 g of a target compound was obtained (99% yield) by the
same manner as described in Example 58, except that
{4-[1-methyl-7-(1l-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-a]q-
uinoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester (2.1 g,
4.2 mmol) prepared in Example 220 was used.
[1242] Mass (M+H.sup.+): 401.2
[1243] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.61 (m, 2H), 1.71 (m,
2H), 2.83 (m, 2H), 3.06 (s, 3H), 3.58 (m, 2H), 3.97 (s, 3H), 7.41
(m, 2H), 7.65 (brs, 3H), 7.78 (m, 3H), 8.04 (s, 1H), 8.30 (d, 1H),
8.43 (t, 1H).
<Example 222> Preparation of
3-methyl-N-{4-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-ylamino]-butyl}-butyramide
##STR00273##
[1245] A target compound was obtained (89% yield) by the same
manner as described in Example 37, except that
N.sup.1-[1-methyl-7-(1-methyl-1H-benzoimidazole-2-yl)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid
prepared in Example 221 was used.
[1246] Mass (M+H.sup.+): 485.3
[1247] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.77 (d, 6H), 1.46
(m, H), 1.66 (m, 2H), 1.86 (d, 2H), 1.89 (m, 1H), 3.05 (s, 3H),
3.07 (m, 2H), 3.55 (q, 2H), 3.92 (s, 3H), 7.23 (t, 1H), 7.28 (t,
1H), 7.60 (d, 1H), 7.67 (d, 1H), 7.70 (t, 1H), 7.74 (dd, 1H), 7.99
(d, 1H), 8.23 (d, 1H), 8.27 (t, 1H).
[1248] The compounds shown in Table 16 below were prepared by the
same manner as described in Examples 220.about.222.
TABLE-US-00016 TABLE 16 Example Structure Name Data Example 223
##STR00274## 3-methyl-N- {4-[1- methyl-7-(5- methyl-1H- benzoimida-
zole-2-yl)- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}- butyramide Mass (M + H.sup.+): 485.3; .sup.1H NMR (500 MHz,
DMSO- d6): .delta.0.78 (d, 6H), 1.48 (m, 2H), 1.67 (m, 2H), 1.87
(d, 2H), 1.89 (m, 1H), 2.40 (s, 3H), 3.03 (s, 3H), 3.07 (q, 2H),
3.55 (m, 2H), 7.00 (d, 1H), 7.34 (brs, 1H), 7.45 (brs, 1H), 7.72
(t, 1H), 8.08 (d, 1H), 8.18 (d, 1H), 8.26 (t, 1H), 8.34 (s, 1H),
12.88 (brs, 1H). Example 224 ##STR00275## N-{4-[7-(1H- benzo-
imidazole-2- yl)-1-methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-3- methyl- butyramide Mass (M + H.sup.+): 471.3;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.79 (d, 6H), 1.47 (m, 2H),
1.67 (m, 2H), 1.87 (d, 2H), 1.89 (m, 1H), 3.04 (s, 3H), 3.06 (q,
2H), 3.54 (q, 2H), 7.20 (t, 2H), 7.58 (d, 2H), 7.72 (t, 1H), 8.08
(d, 1H), 8.21 (d, 1H), 8.29 (t, 1H), 8.38 (s, 1H), 13.02 (s, 1H).
Example 225 ##STR00276## N-{4-[7-(1H- benzo- imidazole-2-
yl)-1-methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}-2-(S)- hydroxy-3- methyl- butyramide Mass (M + H.sup.+):
487.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.67 (d, 3H), 0.83
(d, 3H), 1.23 (m, 1H), 1.50 (m, 2H), 1.66 (m, 2H), 1.93 (m, 1H),
3.05 (s, 3H), 3.09 (m, 1H), 3.15 (m, 1H), 3.55 (q, 2H), 3.61 (s,
1H), 7.34 (d, 2H), 7.69 (m, 3H), 8.10 (d, 1H), 8.27 (d, 1H), 8.42
(brm, 2H). Example 226 ##STR00277## N-{4-[7-(1H- benzo-
imidazole-2- yl)-1-methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-2-(R)- hydroxy-3- methyl- butyramide Mass (M +
H.sup.+): 487.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.67 (d,
3H), 0.83 (d, 3H), 1.23 (m, 1H), 1.50 (m, 2H), 1.66 (m, 2H), 1.93
(m, 1H), 3.05 (s, 3H), 3.09 (m, 1H), 3.15 (m, 1H), 3.55 (q, 2H),
3.61 (s, 1H), 7.34 (d, 2H), 7.69 (m, 3H), 8.10 (d, 1H), 8.27 (d,
1H), 8.42 (brm, 2H). Example 227 ##STR00278## N-{4-[7-(5,6-
dimethoxy- 1H-benzo- imidazole-2- yl)-1-methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3- methyl- butyramide
Mass (M + H.sup.+): 531.3; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.0.77 (d, 6H), 1.47 (m, H), 1.67 (m, 2H), 1.87 (d, 2H), 1.90
(m, 1H), 3.03 (s, 3H), 3.06 (q, 2H), 3.54 (q, 2H), 3.79 (s, 6H),
6.95 (m, 1H), 7.20 (m, 1H), 7.72 (t, 1H), 8.03 (d, 1H), 8.15 (d,
1H), 8.24 (t, 1H), 8.28 (d, 1H), 12.75 (s, 1H). Example 228
##STR00279## {4-[1-methyl- 7-(1-methyl- 1H-benzo- imidazole-2-
yl)-[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
carbamic acid propylester Mass (M + H.sup.+): 487.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.80 (t, 3H), 1.48 (m, 4H), 1.69 (m,
2H), 3.02 (q, 2H), 3.05 (s, 3H), 3.59 (q, 2H), 3.83 (t, 3H), 3.92
(s, 3H), 6.78 (brm, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.58 (d, 1H),
7.67 (d, 1H), 7.74 (d, 1H), 8.01 (s, 2H), 8.23 (d, 1H). Example 229
##STR00280## {4-[1-methyl- 7-(1-methyl- 1H-benzo- imidazole-2-
yl)-[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
carbamic acid cyclopent- ylester Mass (M + H.sup.+): 513.3; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.1.44~ 1.52 (m, 8H), 1.64 (m, 4H),
2.98 (q, 2H), 3.04 (s, 3H), 3.54 (q, 2H), 3.92 (s, 3H), 4.85 (m,
1H), 6.94 (t, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.60 (d, 1H), 7.67
(d, 1H), 7.75 (d, 1H), 8.00 (s, 1H), 8.22 (d, 1H), 8.27 (t, 1H).
Example 230 ##STR00281## 2,2-dimethyl- N-{4-[1- methyl-7-(1-
methyl-1H- benzoimid- azole-2-yl)- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- propionamide Mass (M + H.sup.+):
485.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.01 (s, 9H), 1.48
(m, 2H), 1.62 (m, 2H), 3.04 (s, 3H), 3.06 (q, 2H), 3.54 (q, 2H),
3.92 (s, 3H), 7.23 (t, 1H), 7.28 (t, 1H), 7.39 (t, 1H), 7.60 (d,
1H), 7.67 (d, 1H), 7.72 (d, 1H), 7.99 (s, 1H), 8.22 (d, 1H), 8.28
(t, 1H). Example 231 ##STR00282## acetic acid- 1-{4-[7-(1-
methyl-1H- benzoimid- azole-2-yl)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butylcarbamo- yl}-1-methyl- Mass (M +
H.sup.+): 529.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.38 (s,
6H), 1.47 (m, 2H), 1.64 (m, 2H), 1.92 (s, 3H), 3.04 (s, 3H), 3.07
(q, 2H), 3.55 (q, 2H), 3.92 ethylester (d, 3H), 7.23 (t, 1H), 7.28
(t, 1H), 7.60 (d, 1H), 7.66 (m, 2H), 7.75 (d, 1H), 8.00 (s, 1H),
8.22 (d, 1H), 8.27 (t, 1H). Example 232 ##STR00283## 2-hydroxy-N-
{4-(7-(1- methyl-1H- benzoimid- azole-2-yl)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl}-2- methyl- Mass (M +
H.sup.+): 487.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.17 (s,
6H), 1.50 (m, 2H), 1.64 (m, 2H), 3.03 (s, 3H), 3.09 (q, 2H), 3.55
(q, 2H), 3.92 (s, 3H), 5.26 propionamide (s, 1H), 7.22 (t, 2H),
7.26 (t, 2H), 7.59 (m, 2H), 7.66 (d, 1H), 7.73 (d, 1H), 7.99 (s,
1H), 8.20 (d, 1H), 8.28 (t, 1H). Example 233 ##STR00284##
2,2-difluoro- N-{4-[1- methyl-7-(1- methyl-1H- benzoimid-
azole-2-yl)- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}- butyramide Mass (M + H.sup.+): 507.2; .sup.1H NMR (500 MHz,
DMSO- d6): .delta.0.82 (t, 3H), 1.53 (m, 2H), 1.65 (m, 2H), 1.95
(m, 2H), 3.04 (s, 3H), 3.16 (q, 2H), 3.56 (q, 2H), 3.92 (s, 3H),
7.23 (t, 1H), 7.28 (t, 1H), 7.60 (d, 1H), 7.67 (d, 1H), 7.77 (d,
1H), 7.99 (s, 1H), 8.22 (d, 1H), 8.29 (t, 1H), 8.64 (t, 1H).
Example 234 ##STR00285## 2-(S)- hydroxy-3- methyl-N-{4-
[1-methyl-7- (1-methyl-1H- benzoimid- azole-2-yl)- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+):
501.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.66 (d, 3H), 0.81
(d, 3H), 1.20 (m, 1H), 1.49 (m, 2H), 1.65 (m, 2H), 1.89 (m, 1H),
3.04 (s, 3H), 3.08 butyramide (m, 1H), 3.14 (m, 1H), 3.56 (m, 2H),
3.92 (s, 3H), 5.24 (d, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.60 (d,
1H), 7.61 (m, 2H), 7.74 (d, 1H), 8.00 (s, 1H), 8.23 (d, 1H), 8.30
(t, 1H). Example 235 ##STR00286## 2-(R)- hydroxy-3- methyl-N-{4-
[1-methyl-7- (1-methyl-1H- benzimid- azole-2-yl)- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+):
501.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.66 (d, 3H), 0.80
(d, 3H), 1.20 (m, 1H), 1.65 (m, 2H), 1.89 (m, 1H), 3.04 (s, 3H),
3.08 (m, 1H), 3.14 butyramide (m, 1H), 3.56 (m, 2H), 3.92 (s, 3H),
5.25 (d, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.60 (d, 1H), 7.65 (m,
2H), 7.74 (d, 1H), 7.99 (s, 1H), 8.21 (d, 1H), 8.29 (t, 1H), 7.74
(d, 1H), 7.99 (s, 1H), 8.21 (d, 1H), 8.29 (t, 1H). Example 236
##STR00287## 4-methyl- pentanoic acid-{4-[1- methyl-7-
(1-methyl-1H- benzoimid- azole-2-yl)- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-amide Mass (M + H.sup.+): 499.3;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.74 (d, 6H), 1.36 (m, 2H),
1.38 (m, 1H), 1.45 (m, 2H), 1.65 (m, 2H), 1.98 (t, 2H), 3.04 (s,
3H), 3.05 (m, 2H), 3.56 (q, 2H), 3.92 (s, 3H), 7.23 (t, 1H), 7.28
(t, 1H), 7.60 (d, 1H), 7.67 (d, 1H), 7.71 (m, 2H), 7.09 (s, 1H),
8.22 (d, 1H), 8.28 (t, 1H). Example 237 ##STR00288## 2-methoxy-N-
{4-[1-methyl- 7-(1-methyl- 1H-benzo- imidazole-2- yl)-[1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- benzamide Mass (M +
H.sup.+): 535.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.59 (m,
2H), 1.73 (m, 2H), 3.04 (s, 3H), 3.31 (m, 2H), 3.59 (q, 2H), 3.77
(s, 3H), 3.90 (s, 3H), 6.90 (t, 1H), 7.01 (d, 1H), 7.23 (t, 1H),
7.28 (t, 1H), 7.36 (t, 1H), 7.61 (m, 2H), 7.67 (d, 1H), 7.73 (d,
1H), 7.97 (s, 1H), 8.11 (t, 1H), 8.21 (d, 1H), 8.31 (t, 1H).
Example 238 ##STR00289## 1-isopropyl- 3-{4-[1- methyl-7-(1-
methyl-1H-
benzoimid- azole-2-yl)- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-urea Mass (M + H.sup.+): 486.3; .sup.1H NMR (500
MHz, DMSO- d6): .delta.0.93 (d, 6H), 1.43 (m, 2H), 1.63 (m, 2H),
2.99 (q/ 2H), 3.04 (s, 3H), 3.56 (m, 2H), 3.61 (m, 1H), 3.92 (s,
3H), 5.52 (d, 1H), 5.63 (t, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.60
(d, 1H), 7.67 (d, 1H), 7.74 (d, 1H), 8.00 (s, 1H), 8.22 (d, 1H),
8.29 (t, 1H). Example 239 ##STR00290## 1-cyclohexyl- 3-{4-[1-
methyl-7-(1- methyl-1H- benzoimid- azole-2-yl)- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-urea Mass (M +
H.sup.+): 526.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.98 (m,
3H), 1.17 (m, 3H), 1.42 (m, 3H), 1.52 (m, 2H), 1.64 (m, 4H), 3.00
(q, 2H), 3.04 (s, 3H), 3.55 (q, 2H), 3.92 (s, 3H), 3.58 (d, 1H),
5.64 (t, 1H), 7.23 (t, 1H), 7.28 (t, 1H), 7.60 (d, 1H), 7.67 (d,
1H), 7.75 (d, 1H), 8.00 (s, 1H), 8.22 (d, 1H), 8.31 (t, 1H).
Example 240 ##STR00291## 3-methyl-N- {4-[1-methyl- 7-(1-propyl- 1H-
benzoimid- azole-2-yl)- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- butyramide Mass (M + H.sup.+): 513.3; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.0.71 (t, 3H) 0.77 (d, 6H) 1.45 (m,
2H), 1.68 (m, 4H), 1.86 (d, 2H), 1.88 (m, 1H), 3.04 (s, 3H), 3.06
(m, 2H), 3.54 (m, 2H), 4.30 (m, 2H), 7.15~7.29 (m, 3H), 7.63~7.71
(m, 3H), 7.90 (d, 1H), 8.24 (d, 1H), 8.28 (t, 1H). Example 241
##STR00292## N-(4-{7-[1- (2-methoxy- ethyl)-1H- benzoimid-
azole-2-yl]-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino}- butyl)-3- methyl- Mass (M + H.sup.+): 529.3; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.0.77 (d, 6H), 1.46 (m, 2H), 1.65
(m, 2H), 1.85 (d, 2H), 1.89 (m, 1H), 3.04 (s, 3H), 3.06 (q, 2H),
3.10 butyramide (s, 3H), 3.54 (q, 2H), 3.68 (t, 2H), 4.49 (t, 2H),
7.25 (m, 2H), 7.67 (dd, 2H), 7.71 (t, 2H), 8.00 (s, 1H), 8.22 (d,
1H), 8.28 (t, 1H).
<Preparative Example 18> Preparation of
4-chloro-1-methyl-7-nitro[1,2,4]triazolo[4,3-a]quinoxaline
##STR00293##
[1249] Step 1: Preparation of 2,3-dichloro-6-nitroquinoxaline
[1250] 6-Nitroquinoxaline-2,3-(1H,4H)-dione (12 g, 59.0 mmol),
thionylchloride (28.1 g, 236 mmol) and catalytic amount of
dimethylformamide (0.86 g, 11.8 mmol) were dissolved in
dichloroethane solvent, followed by reflux stirring for 2 hours.
Upon completion of the reaction, the solvent was eliminated. The
temperature was lowered to 0.about.5.degree. C. to solidify the
product. The resulting solid was filtered, and dried under reduced
pressure. As a result, 12.3 g of a target compound was obtained
(87% yield).
[1251] Mass (M+H.sup.+): 244.1
[1252] .sup.1H NMR (300 MHz, DMSO-d6): .delta.8.31 (d, J=9.15 Hz,
1H), 8.60 (d, J=9.15 Hz, 1H), 8.88 (s, 1H).
Step 2: Preparation of
3-chloro-6-nitroquinoxaline-2-ylhydrazine
[1253] 2.3 g of a target compound was obtained (92% yield) by the
same manner as described in step 2 of Preparative Example 2, except
that 2,3-dichloro-6-nitroquinoxaline (2.55 g, 10.5 mmol) prepared
instep 1 of Preparative Example 18 was used.
[1254] Mass (M+H.sup.+): 240.1
Step 3:
4-chloro-1-methyl-7-nitro[1,2,4]triazolo[4,3-a]quinoxaline
[1255] 1.2 g of a target compound was obtained (44% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that 3-chloro-6-nitroquinoxaline-2-ylhydrazine (2.5 g, 10.4 mmol)
prepared in step 2 of Preparative Example 18 was used.
[1256] Mass (M+H.sup.+): 264.0
<Example 242> Preparation of
[4-(1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester
##STR00294##
[1258] 1.3 g of a target compound was obtained (83% yield) by the
same manner as described in Example 57, except that
4-chloro-1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline (1.03
g, 3.91 mmol) prepared in step 3 of Preparative Example 18 was
used.
[1259] Mass (M+H.sup.+): 416.2
[1260] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.45-1.51 (m, 2H), 1.64-1.70 (m, 2H), 2.96-3.00 (m, 2H), 3.03 (s,
3H), 3.53-3.57 (m, 2H), 6.81 (t, J=5.05 Hz, 1H), 8.02 (dd, J=9.05
Hz, 2.40 Hz, 1H), 8.20 (d, J=2.00 Hz, 1H), 8.23 (d, J=9.10 Hz, 1H),
8.60 (t, J=5.45 Hz, 1H).
<Example 243> Preparation of
[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester
##STR00295##
[1262]
[4-(1-Methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester prepared in Example 242 and
Pd/C (10 W %) were dissolved in ethanol, followed by stirring in
the presence of hydrogen gas at 5 bar for 3 hours. As a result, a
target compound obtained (quantitative yield).
[1263] Mass (M+H.sup.+): 386.2
[1264] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.40-1.47 (m, 2H), 1.58-1.65 (m, 2H), 2.93-2.98 (m, 5H), 3.48-3.50
(m, 2H), 5.28 (s, 2H), 6.77 (s, 2H), 7.76 (d, J=8.76 Hz, 1H), 7.85
(t, J=4.53 Hz, 1H).
<Example 244> Preparation of
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide
##STR00296##
[1266] 4-Chloro-1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline
(1.03 g, 3.91 mmol) prepared in step 3 of Preparative Example 18
was dissolved in 20 ml of isopropylalcohol, to which
diisopropylethylamine (0.74 ml, 3.4 mmol) and
N-(4-aminobutyl)-3-methyl-butyramide ditrifluoroacetic acid (2.34
g, 5.86 mmol) were added, followed by reflux stirring for 18 hours.
Upon completion of the reaction, the resulting solid was filtered
and dried under reduced pressure. As a result, 1.3 g of a target
compound was obtained (83% yield).
[1267] Mass (M+H.sup.+): 400.2
[1268] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.46 (m,
2H), 1.65 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 3.01 (s, 3H), 3.05
(q, 2H), 3.54 (q, 2H), 7.781 (t, 1H), 8.05 (d, 1H), 8.22 (s, 1H),
8.26 (d, 1H), 8.59 (t, 1H).
<Example 245> Preparation of
N-[4-(7-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide
##STR00297##
[1270] 0.72 g of a target compound was obtained (78% yield) by the
same manner as described in Example 243, except that
3-methyl-N-[4-(1-methyl-7-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide (1 g, 2.5 mmol) prepared in Example 244 was
used.
[1271] Mass (M+H.sup.+): 370.0
[1272] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.44 (m,
2H), 1.61 (m, 2H), 1.86 (d, 2H), 1.95 (m, 1H), 2.89 (s, 3H), 3.04
(q, 2H), 3.27 (d, 2H), 3.47 (q, 2H), 6.73 (t, 1H), 7.69 (d, 1H),
7.73 (d, 1H), 7.92 (t, 1H), 8.41 (s, 1H).
[1273] The compounds shown in Table 17 below were prepared by using
the compound prepared by the same manner as described in Examples
243.about.245 as an intermediate.
TABLE-US-00017 TABLE 17 Example Structure Name Data Example 246
##STR00298## [4-(7-iso- butyramido- 1-methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic acid-
tert-butylester Mass (M + H.sup.+): 456.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.13 (d, J = 6.80 Hz, 6H), 1.36 (s, 9H), 1.45-
1.48 (m, 2H), 1.62- 1.68 (m, 2H), 2.60- 2.65 (m, 1H), 2.94- 2.98
(m, 2H), 3.00 (s, 3H), 3.52-3.53 (m, 2H), 6.81 (t, J = 5.10 Hz,
1H), 7.47 (dd, J = 9.05 Hz, 1.76 Hz, 1H), 7.99 (d, J = 1.85 Hz,
1H), 8.02 (d, J = 9.00 Hz, 1H), 8.13 (t, J = 5.60 Hz, 1H), 9.98 (s,
1H). Example 247 ##STR00299## N-[4-(7-iso- butyramido- 1-methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-2,2-
dimethyl- propionamide Mass (M + H.sup.+): 440.6; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.07 (s, 9H), 1.13 (d, J = 6.75 Hz, 6H),
1.46-1.52 (m, 2H), 1.62-1.68 (m, 2H), 2.60-2.65 (m, 1H), 3.00 (s,
3H), 3.07- 3.11 (m, 2H), 3.52- 3.56 (m, 2H), 7.43 (t, J = 5.40 Hz,
1H), 7.47 (dd, J = 9.95 Hz, 2.45 Hz, 1H), 7.99 (d, J = 1.55 Hz,
1H), 8.02 (d, J = 9.05 Hz, 1H), 8.13 (brs, 1H), 9.98 (s, 1H).
Example 248 ##STR00300## N-[4-(7-iso- butyramido- 1-methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 460.7; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.13 (d, J = 6.80 Hz, 6H), 1.60-1.66 (m, 2H), 1.71-1.77 (m,
2H), 2.60-2.65 (m, 1H), 3.00 (s, 3H), 3.30- 3.33 (m, 2H), 3.56-
3.60 (m, 2H), 7.42- 7.52 (m, 4H), 7.82 (d, J = 7.40 Hz, 2H), 7.99
(d, J = 2.10 Hz, 1H), 8.02 (d, J = 9.05 Hz, 1H), 8.15 (t, J = 5.70
Hz, 1H), 8.46 (t, J = 5.50 Hz, 1H). Example 249 ##STR00301## [4-(7-
acetylamino- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid- tert-butylester Mass (M +
H.sup.+): 427.7; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (s,
9H), 1.44-1.48 (m, 2H), 1.62-1.66 (m, 2H), 2.09 (s, 3H), 2.94-2.98
(m, 2H), 3.01 (s, 3H), 3.52-3.54 (m, 2H), 6.81 (brs, 1H), 7.43 (d,
J = 8.75 Hz, 1H), 7.98 (s, 1H), 8.01 (d, J = 8.95 Hz, 1H), 8.13 (t,
J = 5.40 Hz, 1H), 10.1 (s, 1H). Example 250 ##STR00302## N-[4-(7-
acetylamino- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-2,2- dimethyl- propionamide Mass (M + H.sup.+):
411.6; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.07 (s, 9H),
1.47-1.50 (m, 2H), 1.62-1.68 (m, 2H), 2.09 (s, 3H), 3.00 (s, 3H),
3.07-3.11 (m, 2H), 3.52-3.56 (m, 2H), 7.41-7.44 (m, 2H), 7.98 (d, J
= 2.15 Hz, 1H), 8.02 (d, J = 9.05 Hz, 1H), 8.12 (brs, 1H), 10.1 (s,
1H). Example 251 ##STR00303## N-[4-(7- acetylamino- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 432.3; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.57- 1.71 (m, 4H), 2.09 (s, 3H), 3.00 (s, 3H), 3.30-3.35
(m, 2H), 3.53-3.56 (m, 2H), 7.42-7.45 (m, 2H), 7.49-7.52 (m, 1H),
7.81-7.83 (m, 1H), 7.97-7.99 (m, 1H), 8.03 (dd, J = 9.00 Hz, 2.25
Hz, 1H), 8.14 (t, J = 5.55 Hz, 1H), 8.46 (t, J = 5.70 Hz, 1H), 10.1
(s, 1H). Example 252 ##STR00304## 3-methyl-N- [4-(1-methyl- 7-
methylamino- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]- butyramide Mass (M + H.sup.+): 384.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 1.48 (m, 2H), 1.66 (m, 2H), 1.86 (d,
2H), 1.87 (m, 1H), 3.09 (s, 3H), 3.07 (q, 2H), 3.57 (q, 2H), 7.70
(m, 3H), 8.11 (s, 1H), 8.34 (d, 1H), 8.54 (t, 1H). Example 253
##STR00305## 3-methyl-N- [4-(1-methyl- 7- propylamino- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- butyramide Mass (M +
H.sup.+): 412.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.91 (d,
6H), 1.02 (m, 2H), 1.24 (m, 2H), 1.67 (m, 3H), 1.75 (m, 2H), 2.02
(m, 2H), 3.03 (s, 3H), 3.16 (q, 2H), 3.35 (m, 3H), 3.70 (t, 2H),
5.71 (t, 1H), 6.40 (t, 1H), 6.56 (d, 1H), 6.89 (s, 1H), 7.71 (d,
1H). Example 254 ##STR00306## N-{4-[7-(3- cyano- propylamino)-
1-methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}-3- methyl- Mass (M + H.sup.+): 437.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.80 (d, 6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.83 (m,
2H), 1.86 (d, 2H), 1.87 (m, 1H), 2.58 (q, 2H), 2.90 (s, 3H), 3.03
butyramide (q, 2H), 3.13 (m, 2H), 3.48 (m, 2H), 5.91 (t, 1H), 6.57
(d, 1H), 6.66 (s, 1H), 7.69 (t, 1H), 7.79 (d, 1H), 7.86 (t, 1H).
Example 255 ##STR00307## N-{4-[7-(3- isopropyl- ureido)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3- methyl-
Mass (M + H.sup.+): 455.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.79 (d, 6H), 1.08 (d, 6H), 1.45 (m, 2H), 1.62 (m, 2H), 1.86
(d, 2H), 1.87 (m, 1H), 2.93 (s, 3H), 3.10 (q, 2H), 3.48 butyramide
(q, 2H), 3.75 (m, 1H), 7.17 (t, 1H), 7.50 (d, 1H), 7.72 (d, 1H),
7.88 (s, 1H), 7.94 (t, 1H), 8.00 (d, 1H), 8.45 (s, 1H). Example 256
##STR00308## N-{4-[7-(3- isopropyl- thioureido)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3- methyl-
Mass (M + H.sup.+): 471.0; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.80 (d, 6H), 1.14 (d, 6H), 1.43 (m, 2H), 1.62 (m, 2H), 1.87
(d, 2H), 1.90 (m, 1H), 2.96 (s, 3H), 3.04 (q, 2H), 3.50 butyramide
(q, 2H), 4.37 (t, 1H), 7.34 (d, 1H), 7.71 (m, 3H), 7.98 (d, 1H),
8.07 (s, 1H), 9.43 (s, 1H). Example 257 ##STR00309## N-[4-(7-
methanesul- fonylamino- 1-methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M + H.sup.+):
448.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45
2H) 1.63 (m, 2H) 1.86 (d, 2H) 1.87 (m, 1H), 2.69 (q, 2H) 2.85 (s,
3H) 2.97 (q, 2H) 3.02 (s, 3H) butyramide 7.51 (d, 1H) 7.69 (t, 1H),
7.91 (s, 1H), 8.09 (d, 1H), 8.30 (t, 1H), 11.34 (s, 1H). Example
258 ##STR00310## 3-methyl-N- {4-[1-methyl- 7-2,2,2- trifluoro-
ethanesulfon- ylamino)- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- Mass (M - H.sup.+): 514.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.70 (d, 6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.86 (d,
2H), 1.87 (m, 1H), 2.90 (s, 2H), 2.97 (q, 2H), 3.32 (s, 3H), 3.51
butyl}- (q, 2H), 6.96 (t, butyramide 1H), 7.13 (t, 1H), 7.46 (d,
1H), 7.53 (s, 1H), 7.70 (d, 1H), 8.04 (t, 1H). Example 259
##STR00311## 3-methyl-N- {4-[1-methyl- 7-(propane-2- sulfonyl-
amino)- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
Mass (M + H.sup.+): 476.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.79 (d, 6H), 1.44 (m, 2H), 1.63 (m, 2H), 1.86 (d, 2H), 1.88
(m, 1H), 2.69 (s, 3H), 2.85 (d, 3H), 2.94 (q, 2H), 2.98 butyramide
(q, 2H), 3.51 (m, 1H), 3.70 (q, 2H), 7.51 (d, 1H), 7.70 (t, 1H),
8.08 (t, 1H), 8.10 (d, 1H), 11.36 (s, 1H).
<Example 260> Preparation of
[4-(7-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00312##
[1275] The compound of Example 260 can be prepared by the following
two-step reaction.
##STR00313##
Step 1: Preparation of
tert-butyl-(4-{[7-(methoxymethyl)carbamoyl]-1-methyl-[1,2,4]triazolo[4,3--
a]quinoxaline-4-ylamino}-butyl)-carbamate
[1276]
4-[(4-Tert-butoxycarbamoylamino)-butylamino]-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-7-carboxylic acid (0.30 g, 0.72 mmol) prepared
in Example 200, methoxylmethylamine hydrochloride (0.08 g, 0.86
mmol), HCTU (0.36 g, 0.86 mmol) and DIPEA (0.38 mL, 2.16 mmol) were
dissolved in dimethylformamide, followed by stirring at room
temperature for 3 hours. Upon completion of the reaction, the
reactant was extracted with ethylacetate and sodium bicarbonate
aqueous solution. The organic layer was washed with 1 N aqueous
hydrochloric acid solution and brine. The reactant was purified by
MPLC (isopropyl alcohol/dichloromethane). As a result, a target
compound was obtained (quantitative yield).
[1277] Mass (M+H.sup.+): 444.1
Step 2: Preparation of
{4-[7-(4-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino]-b-
utyl}-carbamic acid-tert-butylester
[1278]
Tert-butyl-(4-{[7-(methoxymethyl)carbamoyl]-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino}-butyl)-carbamate (0.10 g, 0.22 mmol)
prepared in step 1 was dissolved in anhydrous tetrahydrofuran, to
which excessive amount of 4-methoxyphenylmagnesiumbromide was added
in the presence of nitrogen, followed by reflux stirring for 15
minutes. The reaction was terminated by adding 1 N aqueous
hydrochloric acid solution at room temperature and the reactant was
extracted with ethylacetate. The collected organic layer was washed
with brine, dried over magnesium sulfate, and then purified by MPLC
(isopropyl alcohol/dichloromethane). As a result, a target compound
was obtained (78% yield).
[1279] Mass (M+H.sup.+): 474.5
[1280] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.45-1.52 (m, 2H), 1.62-1.70 (m, 2H), 2.94-3.00 (m, 2H), 3.08 (s,
3H), 3.53-3.60 (m, 2H), 6.79 (brs, 1H), 7.60-7.76 (m, 3H),
7.79-7.82 (m, 2H), 7.88 (d, J=1.77 Hz, 1H), 8.27 (d, J=8.64 Hz,
1H), 8.26 (brs, 1H), 8.48 (brs, 1H)
[1281] The compounds shown in Table 18 below were prepared by the
same manner as described in Example 260.
TABLE-US-00018 TABLE 18 Example Structure Name Data Example 261
##STR00314## {4-[7-(4- chloro- benzoyl)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic Mass (M +
H.sup.+): 508.9; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.34 (s,
9H), 1.43-1.47 (m, 2H), 1.62-1.69 (m, 2H), 2.94-2.98 (m, 2H), 3.06
(s, 3H), 3.53-3.55 (m, 2H), 6.77 (brs, acid-tert- 1H), 7.63-7.69
(m, butylester 3H), 7.79-7.84 (m, 3H), 8.26 (d, J = 8.49 Hz, 1H),
8.36 (brs, 1H). Example 262 ##STR00315## {4-[7-(4- methoxy-
benzoyl)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- carbamic Mass (M + H.sup.+): 504.8; .sup.1H NMR
(300 MHz, CDCl.sub.3): .delta.1.35 (s, 9H), 1.54-1.58 (m, 2H),
1.66-1.76 (m, 2H), 3.06 (s, 3H), 3.09-3.15 (m, 2H), 3.61-3.78 (m,
2H), 3.84 (s, 3H), 4.62 acid-tert- (brs, 1H), 6.42 butylester (brs,
1H), 6.93 (d, J = 8.76 Hz, 2H), 7.65 (dd, J = 8.52 Hz, 1.74 Hz,
1H), 7.80 (d, J = 8.79 Hz, 2H), 7.99 (d, J = 8.61 Hz, 1 H), 8.03
(d, J = 1.74 Hz, 1H).
<Preparative Example 19> Preparation of
4-chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
and
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxalin-
e
##STR00316##
[1283]
4-Chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine (a) and
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
(b) were prepared by the same manner as described in Preparative
Example 5.
Step 1: Preparation of
2,3-dichloro-6-trifluoromethoxy-quinoxaline
[1284] Mass (M+H.sup.+): 283.0
Step 2: Preparation of
(3-chloro-7-trifluoromethoxy-quinoxaline-2-yl)-hydrazine and
(3-chloro-6-trifluoromethoxy-quinoxaline-2-yl)-hydrazine
mixture
[1285] (3-Chloro-7-trifluoromethoxy-quinoxaline-2-yl)-hydrazine and
(3-chloro-6-trifluoromethoxy-quinoxaline-2-yl)-hydrazine mixture
was prepared by the same manner as described in step 2 of
Preparative Example 5, except that
2,3-dichloro-6-trifluoromethoxy-quinoxaline (4.5 g, 16 mmol)
prepared in step 1 of Preparative Example 19 was used. The two
compounds proceeded to the next reaction in the form of a mixture,
followed by separation and purification.
[1286] Mass (M+H.sup.+): 279.0
Step 3: Preparation of
4-chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
(a) and
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinox-
aline (b)
[1287]
4-Chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxal-
ine (a) and
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
(b) mixture was prepared by the same manner as described in step 3
of Preparative Example 5 except that
(3-chloro-7-trifluoromethoxy-quinoxaline-2-yl)-hydrazine and
(3-chloro-6-trifluoromethoxy-quinoxaline-2-yl)-hydrazine mixture
(4.4 g, 15.7 mmol) prepared in step 2 of Preparative Example 19 was
used. The reaction mixture was purified by column chromatography
and as a result 2.8 g (58% yield) of a target compound (a) and 1 g
(21% yield) of another target compound (b) were obtained.
(a).
4-chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxalin-
e
[1288] Mass (M+H.sup.+): 303.1
[1289] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.08 (s, 3H), 7.73
(d, 1H), 8.14 (s, 1H), 8.19 (d, 1H).
(b).
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxalin-
e
[1290] Mass (M+H.sup.+): 303.1
<Example 263> Preparation of
[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester
##STR00317##
[1292] 690 mg of a target compound was obtained (90% yield) by the
same manner as described in Example 57, except that
4-chloro-1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
(a) (510 mg, 1.69 mmol) prepared in step 3 of Preparative Example
19 was used as a starting material.
[1293] Mass (M+H.sup.+): 455.3
[1294] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.43 (m,
1H), 1.61 (m, 1H), 2.92 (q, 2H), 2.98 (s, 3H), 3.49 (q, 1H), 6.74
(t, 1H), 7.41 (d, 1H), 7.64 (d, 1H), 7.92 (s, 1H), 8.27 (t,
1H).
<Example 264> Preparation of
N.sup.1-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid
##STR00318##
[1296] 710 mg of a target compound was obtained (81% yield) by the
same manner as described in Example 58, except that
[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester (690 mg, 1.52 mmol)
prepared in Example 253 was used.
[1297] Mass (M+H.sup.+): 355.3
[1298] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.60 (m, 2H), 1.68 (m,
2H), 2.79 (m, 2H), 2.99 (s, 3H), 3.54 (q, 2H), 7.45 (t, 1H), 7.65
(d, 1H), 7.79 (brm, 2H), 7.94 (d, 1H), 8.33 (t, 1H).
<Example 265> Preparation of
2,2-dimethyl-N-[4-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide
##STR00319##
[1300] 140 mg of a target compound was obtained (74% yield) by the
same manner as described in Example 59, except that
N.sup.1-(1-methyl-8-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid (250 mg, 0.43 mmol)
prepared in Example 264 was used.
[1301] Mass (M+H.sup.+): 437.2
[1302] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.02 (s, 9H), 1.45 (m,
2H) 1.60 (m, 2H), 2.98 (s, 3H), 3.03 (q, 2H), 3.50 (q, 2H), 7.36
(t, 1H), 7.42 (d, 1H), 7.63 (d, 1H), 7.92 (d, 1H), 8.27 (t,
1H).
[1303] The compounds shown in Table 19 below were prepared by the
same manner as described in Example 265.
TABLE-US-00019 TABLE 19 Exam- ple Structure Name Data Exam- ple 266
##STR00320## 3,3- dimethyl-N- [4-(1-methyl-8- trifluoromethoxy-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-butyramide
Mass (M + H.sup.+): 453.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.90 (s, 9H), 1.44 (m, 2H), 1.63 (m, 2H), 1.87 (s, 2H), 2.98
(s, 3H), 3.04 (m, 2H), 3.50 (q, 2H), 7.42 (t, 1H), 7.63 (d, 1H),
7.92 (s, 1H), 8.29 (t, 1H). Exam- ple 267 ##STR00321##
N-[4-(1-methyl-8- trifluoromethoxy- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-benzamide Mass (M + H.sup.+):
459.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.69
(m, 2H), 2.98 (s, 3H), 3.28 (q, 2H), 3.55 (q, 2H), 7.37 (m, 3H),
7.40 (m, 1H), 7.48 (m, 1H), 7.62 (d, 1H), 7.77 (t, 2H), 7.92 (s,
1H), 8.29 (t, 1H), 8.39 (t, 1H). Exam- ple 268 ##STR00322##
2-chloro-N-[4-(1- methyl-8- trifluoromethoxy- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- benzamide Mass (M +
H.sup.+): 493.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.57 (m,
2H), 1.72 (m, 2H), 2.98 (s, 3H), 3.25 (q, 2H), 3.55 (m, 2H), 7.33
(m, 3H), 7.42 (d, 2H), 7.64 (d, 1H), 7.92 (d, 1H), 8.32 (t, 1H),
8.35 (t, 1H).
<Example 269> Preparation of
[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester
##STR00323##
[1305] 4.5 g of a target compound was obtained (93% yield) by the
same manner as described in Example 57, except that
4-chloro-1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline
(b) (1 g, 3.3 mmol) prepared in step 3 of Preparative Example 19
was used as a starting material.
[1306] Mass (M+H.sup.+): 455.3
[1307] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.42 (m,
2H), 1.61 (m, 2H), 2.92 (q, 2H), 2.98 (s, 3H), 3.50 (q, 2H), 7.23
(t, 1H), 7.45 (d, 1H), 7.67 (s, 1H), 8.14 (d, 1H), 8.40 (t,
1H).
<Example 270> Preparation of
N.sup.1-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid
##STR00324##
[1309] 1.3 g of a target compound was obtained (71% yield) by the
same manner as described in Example 58, except that
[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester (1.2 g, 2.64 mmol)
prepared in Example 269 was used.
[1310] Mass (M+H.sup.+): 355.1
[1311] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.60 (m, 2H), 1.68
(m, 2H), 2.80 (m, 2H), 2.98 (s, 3H), 3.54 (q, 2H), 7.25 (t, 1H),
7.45 (s, 1H), 7.72 (brm, 2H), 8.16 (d, 1H), 8.46 (t, 1H).
<Example 271> Preparation of
2,2-dimethyl-N-[4-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-propionamide
##STR00325##
[1313] 120 mg of a target compound was obtained (63% yield) by the
same manner as described in Example 59, except that
N.sup.1-(1-methyl-7-trifluoromethoxy-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl)-butane-1,4-diamine ditrifluoroacetic acid (250 mg, 0.43 mmol)
prepared in Example 270 was used.
[1314] Mass (M+H.sup.+): 439.2
[1315] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.45
(m, 2H) 1.61 (m, 2H), 2.98 (s, 3H), 3.05 (q, 2H), 3.50 (q, 2H),
7.23 (d, 1H), 7.36 (t, 1H), 7.43 (s, 1H), 8.14 (d, 1H), 8.40 (t,
1H).
[1316] The compounds shown in Table 20 below were prepared by the
same manner as described in Example 271.
TABLE-US-00020 TABLE 20 Example Structure Name Data Example 272
##STR00326## 3,3-dimethyl-N- [4-(1-methyl-7- trifluoromethoxy-
[1,2,4]tri- azolo[4,3-a]quin- oxaline-4- ylamino)-butyl]-
butyramide Mass (M + H.sup.+): 453.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.87 (s, 9H), 1.43 (m, 2H), 1.63 (m, 2H), 1.87 (s,
2H), 2.98 (s, 3H), 3.03 (m, 2H), 3.51 (q, 2H), 7.22 (d, 1H), 7.43
(s, 1H), 7.64 (t, 1H), 8.15 (d, 1H), 8.40 (t, 1H). Example 273
##STR00327## N-[4-(1-methyl-7- trifluoromethoxy- [1,2,4]tri-
azolo[4,3-a]quin- oxaline-4- ylamino)-butyl]- benzamide Mass (M +
H.sup.+): 459.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m,
2H), 1.70 (m, 2H), 2.98 (s, 3H), 3.28 (m, 2H), 3.55 (q, 2H), 7.21
(d, 1H), 7.42 (brm, 4H), 7.77 (d, 2H), 8.14 (d, 3H), 8.40 (t, 2H).
Example 274 ##STR00328## 2-chloro-N-[4-(1- methyl-7-
trifluoromethoxy- [1,2,4]tri- azolo[4,3-a]quin- oxaline-4-
ylamino)-butyl]- benzamide Mass (M + H.sup.+): 493.1; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.57 (m, 2H), 1.72 (m, 2H), 2.98 (s,
3H), 3.24 (q, 2H), 3.55 (q, 2H), 7.23 (d, 1H), 7.40 (brm, 4H), 7.45
(s, 1H), 8.15 (d, 1H), 8.36 (t, 1H), 8.43 (t, 1H).
<Preparative Example 20> Preparation of
4-(3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00329##
[1317] Step 1: Preparation of
[4-(3-chloro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1318] 14.5 g of a target compound was obtained (95% yield) by the
same manner as described in Example 57, except that
2,3-dichloro-6-methoxy-quinoxaline (9.2 g, 40.3 mmol) prepared in
step 1 of Preparative Example 8 was used.
[1319] Mass (M+H.sup.+): 381.0
[1320] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.33 (s, 9H), 1.41 (m,
2H), 1.57 (m, 2H), 2.91 (q, 2H), 3.41 (q, 2H), 3.83 (s, 3H), 6.74
(t, 1H), 6.97 (d, 1H), 6.98 (d, 1H), 7.33 (t, 1H), 7.57 (d,
1H).
Step 2: Preparation of
[4-(3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1321]
[4-(3-chloro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (14.5 g, 38 mmol) prepared in step 1 of
Preparative Example 20 and hydrazine hydrate (73 ml, 1.5 mol) were
dissolved in 150 ml of ethanol, followed by reflux stirring for 3
hours. Upon completion of the reaction, the solvent was distilled
under reduced pressure. The reaction mixture was extracted with
ethylacetate and water. The reactant was dried over magnesium
sulfate, filtered, distilled and dried under reduced pressure. As a
result, 13.5 g of a target compound was obtained (94% yield), which
proceeded to the next reaction without purification.
[1322] Mass (M+H.sup.+): 377.1
<Example 275> Preparation of
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00330##
[1324] 0.65 g of a target compound was obtained (61% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (1 g, 2.7 mmol) prepared in step 2 of
Preparative Example 20 was used.
[1325] Mass (M+H.sup.+): 401.2
[1326] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.60 (m, 2H), 2.90 (q, 2H), 2.94 (s, 3H), 3.50 (q, 2H), 3.80
(s, 3H), 6.75 (t, 1H), 6.85 (d, 1H), 7.06 (s, 1H), 7.95 (d, 1H),
8.08 (t, 1H).
<Example 276> Preparation of
N.sup.1-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid
##STR00331##
[1328] 610 mg of a target compound was obtained (71% yield) by the
same manner as described in Example 58, except that
[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester (650 mg, 1.62 mmol) prepared in
Example 275 was used.
[1329] Mass (M+H.sup.+): 301.1
[1330] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.68
(m, 2H), 2.81 (q, 2H), 2.96 (s, 3H), 3.54 (q, 2H), 3.80 (s, 3H),
6.87 (d, 1H), 7.05 (s, 1H), 7.65 (brm, 2H), 7.97 (d, 1H), 8.20 (t,
1H).
<Example 277> Preparation of
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-2,2-dimethyl-propionamide
##STR00332##
[1332] 41 mg of a target compound was obtained (31% yield) by the
same manner as described in Example 59, except that
N.sup.1-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butan-
e-1,4-diamine ditrifluoroacetic acid (150 mg, 0.28 mmol) prepared
in Example 276 was used.
[1333] Mass (M+H.sup.+): 385.2
[1334] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.02 (s, 9H), 1.45 (m,
2H), 1.60 (m, 2H), 2.95 (s, 3H), 3.05 (q, 2H), 3.49 (q, 2H), 3.80
(s, 3H), 6.85 (d, 1H), 7.05 (s, 1H), 7.37 (t, 1H), 7.95 (s, 1H),
8.08 (t, 1H).
[1335] The compounds shown in Table 21 below were prepared by the
same manner as described in Example 277.
TABLE-US-00021 TABLE 21 Example Structure Name Data Example 278
##STR00333## [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isopropylester
Mass (M + H.sup.+): 387.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.10 (d, 6H), 1.45 (m, 2H), 1.62 (m, 2H), 2.95 (s, 3H), 2.99
(m, 2H), 3.50 (q, 2H), 3.80 (s, 3H), 4.68 (m, 1H), 6.85 (d, 1H),
6.95 (t, 1H), 7.06 (s, 1H), 7.95 (s, 1H), 8.08 (t, 1H). Example 279
##STR00334## [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 401.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80
(d, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.75 (m, 1H), 2.95 (s, 3H),
2.99 (m, 2H), 3.60 (q, 2H), 3.66 (q, 2H), 3.80 (s, 3H), 6.85 (d,
1H), 7.00 (t, 1H), 7.06 (s, 1H), 7.95 (s, 1H), 8.08 (t, 1H).
Example 280 ##STR00335## [4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic acid-sec-
Mass (M + H.sup.+): 401.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.78 (t, 3H), 1.08 (d, 3H), 1.42 (m, 2H), 1.44 (m, 2H), 1.62
(m, 2H), 2.95 (s, 3H), 2.98 (m, 2H), 3.50 (q, 2H), 3.80 (s, 3H),
4.52 (m, 1H), 6.84 (d, butylester 1H), 6.95 (t, 1H), 7.06 (s, 1H),
7.95 (s, 1H), 8.08 (t, 1H). Example 281 ##STR00336## N-[4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- isobutyramide Mass (M + H.sup.+): 371.2.sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.93 (d, 6H), 1.45 (m, 2H), 1.62 (m,
2H), 2.27 (m, 1H), 2.95 (s, 3H), 3.04 (q, 2H), 3.50 (q, 2H), 3.82
(s, 3H), 6.85 (d, 1H), 7.06 (s, 1H), 7.63 (t, 1H), 7.95 (d, 1H),
8.09 (t, 1H). Example 282 ##STR00337## cyclopropane; carboxylic
acid-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-amide Mass (M + H.sup.+): 369.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.55 (m, 2H), 0.60 (m, 2H),
1.46 (m, 3H), 1.63 (m, 2H), 2.95 (s, 3H), 3.07 (q, 2H), 3.52 (q,
2H), 3.80 (s, 3H), 6.84 (t, 1H), 7.07 (d, 1H), 7.95 (s, 1H), 7.96
(d, 1H), 8.10 (t, 1H). Example 283 ##STR00338## butene-2-oic
acid-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-amide Mass (M + H.sup.+): 369.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.1.46 (m, 2H), 1.60 (m, 2H),
1.73 (d, 3H), 2.95 (s, 3H), 3.10 (q, 2H), 3.50 (q, 2H), 3.82 (s,
3H), 5.05 (d, 1H), 5.84 (m, 1H), 6.86 (d, 1H), 7.06 (s, 1H), 7.80
(t, 1H), 7.96 (d, 1H), 8.09 (t, 1H). Example 284 ##STR00339##
3-methyl- butene-2-oic acid-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-amide Mass (M +
H.sup.+): 383.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.45 (m,
2H), 1.63 (m, 2H), 1.71 (s, 3H), 2.02 (s, 3H), 2.94 (s, 3H), 3.07
(m, 2H), 3.52 (m, 2H), 3.80 (s, 3H), 5.57 (s, 1H), 6.83 (d, 1H),
7.05 (s, 1H), 7.67 (m, 1H), 7.92 (d, 1H), 8.09 (m, 1H). Example 285
##STR00340## N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- methyl- butyramide Mass (M +
H.sup.+): 385.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
6H), 1.44 (m, 2H), 1.62 (m, 2H), 1.86 (m, 2H), 1.90 (m, 1H), 2.95
(s, 3H), 3.05 (q, 2H), 3.50 (q, 2H), 3.80 (s, 3H), 6.85 (d, 1H),
7.06 (s, 1H), 7.69 (t, 1H), 7.95 (s, 1H), 8.08 (t, 1H). Example 286
##STR00341## 2-(S)-fluoro- N-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M +
H.sup.+): 403.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
3H), 0.90 (d, 3H), 1.49 (m, 2H), 1.63 (m, 2H), 2.06 (m, 1H), 2.94
(s, 3H), 2.94 (m, 2H), 3.50 (m, 2H), 3.80 (s, 3H), 4.56 (d, 1H),
butyramide 6.82 (d, 1H), 7.03 (s, 1H), 7.91 (d, 1H), 8.09 (m, 1H).
Example 287 ##STR00342## N-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3,3- dimethyl-
butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.86 (s, 3H), 1.45 (m, 2H), 1.63 (m, 2H), 1.88 (s,
2H), 2.95 (s, 3H), 3.04 (q, 2H), 3.50 (q, 2H), 3.80 (s, 3H), 6.85
(d, 1H), 7.06 (s, 1H), 7.64 (t, 1H), 7.96 (d, 1H), 8.09 (t, 1H).
Example 288 ##STR00343## 4-methyl- pentanoic acid-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]-amide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.78 (d, 6H), 1.31 (m, 2H), 1.42 (m, 3H), 1.62 (m,
2H), 1.98 (m, 2H), 2.95 (s, 3H), 3.04 (q, 2H), 3.51 (q, 2H), 3.80
(s, 3H), 6.85 (d, 1H), 7.06 (s, 1H), 7.70 (t, 1H), 7.96 (d, 1H),
8.09 (t, 1H). Example 289 ##STR00344## 3-methyl- pentanoic
acid-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-amide Mass (M + H.sup.+): 399.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 6H), 1.06-1.23
(brm, 2H), 1.44 (m, 2H), 1.63 (m, 2H), 1.78 (m, 2H), 1.97 (m, 1H),
2.95 (s, 3H), 3.05 (q, 2H), 3.50 (q, 2H), 3.81 (s, 3H), 6.85 (d,
1H), 7.06 (s, 1H), 7.70 (t, 1H), 7.96 (s, 1H), 8.09 (t, 1H).
Example 290 ##STR00345## 2-ethyl-N- [4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.72 (m, 6H), 1.26 (m, 2H), 1.36 (m, 2H), 1.47 (m,
2H), 1.63 (m, 2H), 1.86 (m, 1H), 2.95 (s, 3H), 3.07 (q, 2H), 3.51
(q, 2H), 3.80 (s, 3H), 6.86 (d, 1H), 7.05 (s, 1H), 7.72 (t, 1H),
7.96 (d, 1H), 8.10 (t, 1H), Example 291 ##STR00346## N-[4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-2- methyl- butyramide Mass (M + H.sup.+): 385.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.73 (t, 3H), 0.91 (d, 3H),
1.46 (m, 2H), 2.06 (m, 1H), 2.94 (s, 3H), 3.08 (q, 2H), 3.51 (q,
2H), 3.80 (s, 3H), 6.85 (d, 1H), 7.05 (s, 1H), 7.67 (s, 1H), 7.95
(d, 1H), 8.09 (t, 1H), Example 292 ##STR00347## 2,2,3,3,4,4,4-
heptafluoro- N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- Mass (M + H.sup.+): 497.1;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.1.54 (m, 2H), 1.67 (m, 2H),
2.95 (s, 3H), 3.21 (m, 2H), 3.53 (m, 2H), 3.80 (s, 3H), 6.84 (d,
1H), 7.10 (s, 1H), 7.94 (d, 1H), 8.23 (s, 1H), butyramide 9.38 (s,
1H). Example 293 ##STR00348## 3,3,3- trifluoro-N- [4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]-2,2- Mass (M + H.sup.+): 439.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.27 (d, 6H), 1.48 (m, 2H), 1.60 (m, 2H), 2.96 (s,
3H), 3.11 (q, 2H), 3.51 (q, 2H), 3.81 (s, 3H), 6.84 (d, 1H), 7.06
(s, 1H), 7.87 (t, 1H), dimethyl- 7.96 (s, 1H), 8.11 propaneamide
(t, 1H). Example 294 ##STR00349## 2,2-difluoro- N-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
butyramide Mass (M + H.sup.+): 407.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.84 (m, 3H), 1.44 (m, 2H), 1.63 (m, 2H), 1.96 (m,
2H), 2.95 (s, 3H), 3.15 (q, 2H), 3.51 (q, 2H), 3.81 (s, 3H), 6.85
(d, 1H), 7.06 (s, 1H), 7.95 (d, 1H), 8.12 (t, 1H), 8.64 (t, 1H).
Example 295 ##STR00350## 2-(R)- hydroxy-N- [4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
Mass (M + H.sup.+): 373.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.14 (s, 3H), 1.21 (m, 1H), 1.48 (m, 2H), 1.52 (m, 2H), 2.95
(s, 3H), 3.10 (m, 2H), 3.53 (m, 2H), 3.81 (s, 3H), 3.90 (m, 1H),
6.86 (d, 1H), propaneamide 7.11 (s, 1H), 7.66 (m, 1H), 7.96 (d,
1H), 8.35 (s, 1H) Example 296 ##STR00351## acetic acid- 1-[4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butylcar- bamoyl]-1- Mass (M + H.sup.+): 429.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.39 (s, 6H), 1.45 (m, 2H), 1.60 (m,
2H), 1.94 (s, 3H), 2.94 (s, 3H), 3.04 (q, 2H), 3.49 (q, 2H), 3.80
(s, 3H), 6.84 (dd, 1H), 7.06 (s, 1H), methyl- 7.67 (t, 1H), 7.95
ethylester (d, 1H), 8.07 (t, 1H). Example 297 ##STR00352##
2-hydroxy-N- [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-2- methyl- Mass (M + H.sup.+):
387.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.18 (s. 6H), 1.47
(m, 2H), 1.61 (m, 2H), 2.94 (s, 3H), 3.08 (q, 2H), 3.50 (q, 2H),
3.80 (s, 3H), 5.24 (s, 1H), 6.83 (dd, 1H), 7.05 (s, 1H),
propionamide 7.59 (t, 1H), 7.93 (d, 1H), 8.09 (t, 1H). Example 298
##STR00353## 2-(R)- hydroxy-N- [4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M
+ H.sup.+): 401.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d,
3H), 0.84 (d, 3H), 1.48 (m, 2H), 1.63 (m, 2H), 1.95 (m, 1H), 2.95
(s, 3H), 3.10 (m, 2H), 3.51 (m, 2H), 3.60 (s, 1H), 3.81 (s, 3H),
methyl- 6.84 (d, 1H), 7.09 butyramide (s, 1H), 7.66 (m, 1H), 7.94
(m, 1H). Example 299 ##STR00354## 2-(S)- hydroxy-N- [4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-3- Mass (M + H.sup.+): 401.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.68 (m, 3H), 0.84 (m, 3H), 1.48 (m, 2H),
1.63 (m, 2H), 1.91 (m, 1H), 2.47 (s, 3H), 2.95 (s, 3H), 3.14 (m,
2H), 3.60 (m, 2H), 3.61 (s, 1H), methyl- 3.80 (s, 3H), 6.84
butyramide (d, 1H), 7.10 (s, 1H), 7.66 (s, 1H), 7.94 (d, 1H).
Example 300 ##STR00355## 2-(R)- methoxy-N- [4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3-
Mass (M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.45 (m, 2H), 1.63 (m, 2H), 1.71 (s, 3H), 2.02 (d, 3H), 2.94
(s, 3H), 3.07 (m, 2H), 3.29 (s, 4H), 3.50 (m, 2H), 3.80 (s, 3H),
5.57 (s, 1H), methyl- 6.83 (d, 1H), 7.05 butyramide (s, 1H), 7.67
(m, 1H), 7.92 (d, 1H), 8.09 (m, 1H). Example 301 ##STR00356##
2-(S)- methoxy-N- [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+): 415.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 6H), 1.48 (m, 2H),
1.62 (m, 2H), 1.63 (m, 1H), 2.95 (s, 3H), 3.11 (m, 2H), 3.18 (s,
3H), 3.60 (s, 3H), 6.85 (d, 1H), 7.04 (s, 1H), methyl- 7.79 (m,
1H), 7.93 butyramide (d, 1H), 8.10 (m, 1H). Example 302
##STR00357## 2-(S)-bromo- N-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M +
H.sup.+): 463.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.83 (d,
3H), 0.97 (d, 3H), 1.48 (m, 2H),1.63 (m, 2H), 2.03 (m, 1H), 2.95
(s, 3H), 3.10 (m, 2H), 3.50 (m, 2H), 3.81 (s, 3H), 4.03 (d, 1H),
butyramide 6.84 (d, 1H), 7.10 (d, 1H), 7.94 (d, 1H), 8.11 (m, 1H),
8.17 (m, 1H). Example 303 ##STR00358## acetic acid- [4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butylcar- bamoyl]- Mass (M + H.sup.+): 400.4; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.35 (m, 2H), 1.47 (m, 2H), 2.02 (s,
3H), 2.94 (q, 2H), 3.06 (s, 3H), 3.88 (s, 3H), 4.15 (q, 2H), 4.87
(s, 2H), 7.34 (dd, 1H), 7.54 (s, 1H), methylester 7.80 (t, 1H),
7.96 (t, 1H), 8.26 (d, 1H). Example 304 ##STR00359## 2-hydroxy-N-
[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- acetamide Mass (M + H.sup.+): 359.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.19 (br, 1H), 1.47 (m, 2H), 1.62
(m, 2H), 2.94 (s, 3H), 3.12 (q, 2H), 3.51 (q, 2H), 3.74 (d, 2H),
3.84 (s, 3H), 6.85 (d, 1H), 7.06 (s, 1H), 7.69 (t, 1H), 7.96 (d,
1H), 8.09 (t, 1H). Example 305 ##STR00360## N-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
malonamic acid ethylester Mass (M + H.sup.+): 415.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.11- 1.15 (brm, 5H), 1.46 (m, 2H), 1.65
(m, 2H), 2.95 (s, 3H), 3.11 (q, 2H), 3.51 (q, 2H), 3.81 (s, 3H),
4.06 (q, 2H), 6.85 (d, 1H), 7.07 (s, 1H), 7.96 (d, 1H), 8.03 (t,
1H), 8.09 (t, 1H). Example 306 ##STR00361## N-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
malonamic acid Mass (M +
H.sup.+): 387.1; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.46 (m,
2H), 1.64 (m, 2H), 2.95 (s, 3H), 3.08 (q, 2H), 3.31 (q, 2H), 3.52
(q, 2H), 3.81 (s, 3H), 6.85 (d, 1H), 7.11 (t, 1H), 7.95 (d, 1H),
8.02 (t, 1H), 8.19 (br, 1H), 12.40 (br, 1H). Example 307
##STR00362## N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-2- thiophene-2- yl-acetamide Mass
(M + H.sup.+): 425.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.47
(m, 2H), 1.64 (m, 2H), 2.95 (s, 3H), 3.07 (q, 2H), 3.51 (q, 2H),
3.57 (s, 2H), 3.80 (s, 3H), 6.83 (t, 1H), 6.86 (m, 2H), 7.06 (s,
1H), 7.26 (d, 1H), 7.96 (d, 1H), 8.03 (t, 1H), 8.10 (t, 1H).
Example 308 ##STR00363## 2-furan-2-yl- N-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- acetamide
Mass (M + H.sup.+): 409.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.47 (m, 2H), 1.63 (m, 2H), 2.95 (s, 3H), 3.08 (q, 2H), 3.41
(s, 2H), 3.50 (q, 2H), 3.80 (s, 3H), 6.12 (d, 1H), 6.30 (d, 1H),
6.85 (dd, 1H), 7.07 (d, 1H), 7.46 (s, 1H), 7.96 (m, 2H), 8.11 (t,
1H). Example 309 ##STR00364## 3-cyclopentyl- N-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
propionamide Mass (M + H.sup.+): 423.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.97 (brs, 2H), 1.42 (m, 2H), 4.45 (m, 2H), 1.50
(m, 4H), 1.62 (m, 5H), 2.01 (m, 2H), 2.95 (s, 3H), 3.04 (q, 2H),
3.51 (q, 2H), 3.80 (s, 3H), 6.85 (d, 1H), 7.06 (s, 1H), 7.71 (t,
1H), 7.96 (d, 1H), 8.08 (t, 1H), Example 310 ##STR00365## {1-[4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butylcarbamo- yl]-2-methyl- propyl}- Mass (M +
H.sup.+): 500.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.71 (d,
6H), 1.27 (s, 9H), 1.43 (m, 2H), 1.61 (m, 2H), 1.81 (m, 1H), 2.91
(s, 3H), 3.07 (q, 2H), 3.47 (q, 2H), 3.06 (d, 1H), 3.77 (s, 3H),
carbamic 6.46 (d, 1H), 6.82 acid-tert- (d, 1H), 7.02 (s, 1H),
butylester 7.75 (t, 1H), 7.93 (d, 1H), 8.05 (t, 1H). Example 311
##STR00366## 2-amino-N- [4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M +
H.sup.+): 400.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.88 (d,
6H), 1.56 (m, 2H), 1.73 (m, 2H) 2.02 (m, 1H), 2.99 (s, 3H), 3.08
(m, 1H), 3.21 (m, 1H) 3.51 (m, 1H), 3.82 (s, 5H), 7.00 (d, 1H),
8.03 (d, butyramide 1H), 8.18 (s, 2H), 8.61 (s, 1H). Example 312
##STR00367## 2-(R)-di- methylamino- N-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M
+ H.sup.+): 428.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.69 (d,
3H), 0.82 (d, 3H), 1.47 (m, 2H), 1.67 (m, 2H), 1.95 (m, 1H), 2.11
(s, 6H), 2.36 (s, 1H), 2.95 (s, 3H), 3.10 (m, 2H), 3.80 (s, 3H),
6.84 (d, methyl- 1H), 7.05 (s, 1H), butyramide 7.724 (s, 1H), 7.96
(d, 1H), 8.11 (m, 1H). Example 313 ##STR00368## 2-(S)-di-
methylamino- N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+): 428.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.70 (d, 3H), 0.83 (d, 3H),
1.46 (m, 2H), 1.65 (m, 2H), 1.95 (m, 1H), 2.15 (s, 6H), 2.95 (s,
3H), 3.10 (m, 2H), 3.50 (m, 2H), 3.80 (s, 3H), methyl- 6.84 (d,
1H), 7.05 (s, butyramide 1H), 7.94 (s, 1H), 7.96 (d, 1H), 8.12 (m,
1H). Example 314 ##STR00369## N-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3-
methyl-2-(S)- morpholine- Mass (M + H.sup.+): 470.3; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.69 (m, 3H), 0.85 (m, 3H), 1.48 (m,
2H), 1.64 (m, 2H), 1.92 (m, 1H), 2.46 (m, 1H), 2.95 (s, 3H), 3.08
(m, 2H), 3.30 (m, 2H), 3.45 (m, 4H), 4-yl- 3.81 (s, 3H), 6.84
butyramide (d, 1H), 7.06 (d, 1H), 7.79 (m, 1H), 7.96 (d, 1H), 8.11
(m, 1H). Example 315 ##STR00370## 2-(S)-(3- hydroxy- pyrrolidine-1-
yl)-N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+): 470.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.74 (m, 3H), 0.83 (m, 3H),
1.46 (m, 3H), 1.65 (m, 2H), 1.90 (m, 2H), 2.46 (m, 2H), 2.55 (m,
2H), 2.70 (m, 1H), 2.94 (s, 3H), 3.08 (m, 2H), 3.50 (m, 2H), 3.80
methyl- (s, 3H), 4.04 (s, butyramide 1H), 4.56 (s, 1H), 6.83 (d,
1H), 7.03 (d, 1H), 7.71 (s, 1H), 7.91 (d 1H), 8.10 (m, 1H). Example
316 ##STR00371## 2-(S)-(4- hydroxy- piperidine- 1-yl)-N-[4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-3- methyl- Mass (M + H.sup.+): 484.3; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.69 (m, 3H), 0.82 (m, 3H), 1.16 (m,
2H), 1.45 (m, 2H), 1.63 (m, 4H), 1.90 (m, 1H), 2.15 (m, 2H), 2.46
(m, 1H), 2.48 (m, 2H), 2.95 (s, 3H), 3.10 (m, 2H), 3.25 (m, 1H),
3.52 (s, 1H), 3.80 (s, butyramide 3H), 6.85 (d, 1H), 7.05 (d, 1H),
7.71 (s, 1H), 7.94 (d, 1H), 8.11 (m, 1H). Example 317 ##STR00372##
2-(S)-[4-(2- hydroxy- ethyl)- piperidine- 1-yl]-N-[4-(7- methoxy-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3-
methyl- Mass (M + H.sup.+): 512.1; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.68 (m, 3H), 0.80 (m, 3H), 0.90 (m, 1H), 1.05 (m, 2H), 1.15
(m, 1H), 1.22 (m, 2H), 1.45 (m, 4H), 1.55 (m, 2H), 1.90 (m, 1H),
2.02 (m, 2H), 2.40 (d, 1H), 2.64 (m, 2H), 2.95 (s, 3H), 3.00 (m,
2H), butyramide 3.50 (m, 2H), 3.80 (s, 3H), 4.21 (m 1H), 6.84 (d,
1H), 7.05 (m, 1H), 7.68 (s, 1H), 7.94 (d, 1H), 7.96 (m, 1H).
Example 318 ##STR00373## (S)-{1-[4- (7-methoxy- 1-methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butylcarbamo-
yl]-2-methyl- propyl}- Mass (M + H.sup.+): 500.3; .sup.1H NMR (500
MHz, CDCl.sub.3): .delta.0.85 (m, 6H), 0.93 (m, 6H), 1.67 (m, 2H),
1.77 (m, 2H), 1.79 (m, 1H), 2.10 (s, 1H), 3.03 (s, 3H), 3.34 (m,
2H), 3.75 (s, 2H), 3.80 (m, 1H), carbamic acid 3.89 (s, 3H), 3.95
isobutylester (m, 1H), 5.47 (s, 1H), 6.41 (s, 1H), 6.57 (s, 1H),
6.57 (s, 1H), 6.84 (d, 1H), 7.19 (s, 1H), 7.79 (d, 1H). Example 319
##STR00374## (S)-{1-[4- (7-methoxy- 1-methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butylcarbamo- yl]-2-methyl-
propyl}- Mass (M + H.sup.+): 486.3; .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta.0.87 (m, 9H), 1.57 (m, 2H), 1.65 (m, 2H), 1.78
(m, 2H), 2.10 (s, 1H), 2.10 (s, 1H), 3.03 (s, 3H), 3.34 (m, 2H),
3.75 (s, 2H), 3.88 (s, 3H), carbamic acid 3.97 (m, 2H), 5.44
propylester (s, 1H), 6.43 (s, 1H), 6.56 (s, 1H), 6.84 (d, 1H), 7.19
(s, 1H), 7.84 (d, 1H). Example 320 ##STR00375## (S)-{1-[4-
(7-methoxy- 1-methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butylcarbamo- yl]-2-methyl- propyl}- carbamic acid
isopropylester Mass (M + H.sup.+): 486.3; .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta.0.89 (m, 6H), 1.19 (m, 6H), 1.67 (m, 2H), 1.78
(m, 2H), 2.11 (s, 1H), 3.04 (s, 3H), 3.34 (m, 2H), 3.89 (s, 2H),
3.89 (s, 3H), 3.96 (m, 1H), 4.85 (s, 1H), 5.28 (s, 1H), 6.34 (m,
1H), 6.85 (d, 1H), 7.25 (s, 1H), 7.80 (d, 1H). Example 321
##STR00376## (S)-2-(S)- fluoro-N-{1- [4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl carbamoyl]-
2-methyl- Mass (M + H.sup.+): 502.3; .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta.0.89 (m, 9H), 1.05 (m, 3H), 1.71 (m, 2H), 1.82
(m, 2H), 2.10 (m, 1H), 2.25 (m, 1H), 3.02 (s, 3H), 3.34 (m, 2H),
3.76 (s, 2H), 3.87 (s, 3H), 4.30 (m, 1H), 4.74 (d, 1H), 6.85 (m,
propyl}-3- 2H), 7.00 (m, 1H), methyl- 7.35 (m, 1H), 7.72 butyramide
(m, 2H). Example 322 ##STR00377## (S)-N-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3-
methyl-2-(3- methyl- butyryl- amino)- Mass (M + H.sup.+): 484.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 12H), 1.45 (m, 2H),
1.61 (m, 2H), 1.92 (m, 2H), 2.94 (s, 3H), 3.05 (m, 4H), 3.49 (m,
2H), 3.81 (s, 1H), 4.02 (m, 1H), 6.85 (d, 1H), 7.05 (s, 1H), 7.68
(d, 1H), 7.89 (m, 1H), 7.94 (d, 1H), 8.18 (m, butyramide 1H).
Example 323 ##STR00378## (S)-2-(2,2- dimethyl- propionylami-
no)-N-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+): 484.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.74 (m, 6H), 1.05 (s, 9H),
1.45 (m, 2H), 1.63 (m, 2H), 1.90 (m, 2H), 2.94 (s, 3H), 3.05 (m,
2H), 3.49 (m, 2H), 3.80 (s, 3H), 4.04 (m, 1H), 6.84 (d, 1H), 7.00
methyl- (d, 1H), 7.10 (s, butyramide 1H), 7.85 (m, 1H), 7.99 (d,
1H), 8.10 (s, 1H). Example 324 ##STR00379## 2-(S)-(2- (S)-hydroxy-
propionylami- no)-N-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- Mass (M + H.sup.+): 472.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 6H), 1.17 (m, 3H),
1.51 (m, 2H), 1.66 (m, 2H), 1.67 (HI, 1H), 2.98 (s, 6H), 3.05 (m,
2H), 3.82 (s, 3H), 3.92 (m, 2H), 4.10 (s, 1H), 6.99 (d, butyl]-3-
1H), 7.38 (d, 1H), methyl- 7.59 (s, 1H), 8.01 (d, butyramide 1H),
8.15 (m, 1H). Example 325 ##STR00380## (S)-{2-(4- hydroxy-
phenyl)-1- [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl carbamoyl]- ethyl}- carbamic
acid-tert- butylester Mass (M + H.sup.+): 564.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.25 (s, 9H), 1.44 (m, 2H), 1.61 (m, 2H),
2.47 (m, 2H), 2.94 (s, 3H), 3.10 (m, 2H), 3.50 (m, 2H), 3.79 (s,
3H), 3.95 (m, 1H), 6.57 (d, 2H), 6.80 (d, 1H), 6.90 (d, 2H), 7.06
(s, 1H), 7.78 (m, 1H), 7.93 (d, 1H), 8.08 (m, 1H), 9.09 (s, 1H).
Example 326 ##STR00381## 2-(S)-amino- 3-(4- hydroxy- phenyl)-N-
[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- propionamide Mass (M + H.sup.+): 464.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.48 (m, 2H), 1.63 (m, 2H), 2.47 (m,
2H), 3.00 (m, 4H), 3.10 (m, 1H), 3.80 (m, 6H), 6.63 (d, 2H), 6.97
(d, 2H), 7.01 (m, 2H), 8.02 (d, 1H), 8.04 (s, 1H), 8.27 (s, 2H),
8.66 (m, 1H). Example 327 ##STR00382## 2-(S)-meth- anesulfonyl-
amino-N-[4- (7-methoxy- 1-methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M + H.sup.+):
478.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (m, 6H), 1.48
(m, 2H), 1.63 (m, 2H), 1.85 (m, 1H), 2.74 (s, 3H), 2.95 (s, 3H),
3.10 (m, 1H), 3.46 (s, 3H), 3.81 (s, 3H), 6.85 (d, 1H), 7.05 (d,
1H), 7.10 butyramide (d, 1H), 7.95 (d, 1H), 8.05 (d, 1H), 8.10 (d,
1H). Example 328 ##STR00383## 2-fluoro-N- [4-(7- methoxy- 1-methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
benzramide Mass (M + H.sup.+): 423.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.58 (m, 2H), 1.69 (m, 2H), 2.95 (s, 3H), 3.26 (q,
2H), 3.54 (q, 2H), 3.80 (s, 3H) 6.85 (d, 1H), 7.06 (s, 1H), 7.20
(m, 2H), 7.44 (m, 1H), 7.53 (m, 1H), 7.95 (d, 1H), 8.12 (t, 1H),
8.26 (t, 1H). Example 329 ##STR00384## N-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-2- phenyl-
acetamide Mass (M + H.sup.+): 419.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.46 (m, 2H), 1.62 (m, 2H), 2.95 (s, 3H), 3.06 (q,
2H), 3.33 (s, 2H), 3.51 (q, 2H), 3.80 (s, 3H), 6.86 (dd, 1H), 7.06
(d, 1H), 7.19 (m, 1H), 7.20 (m, 4H), 7.97 (m, 2H), 8.09 (t, 1H).
Example 330 ##STR00385## 1-isopropyl- 3-[4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-urea Mass
(M + H.sup.+): 386.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.95
(d, 6H), 1.41 (m, 2H), 1.60 (m, 2H), 2.95 (s, 3H), 2.97 (q, 2H),
3.50 (q, 2H), 3.60 (m, 1H), 3.81 (s, 3H), 5.54 (d, 1H), 5.65 (t,
1H), 6.85 (d, 1H), 7.07 (s, 1H), 7.95 (d, 1H), 8.09 (t, 1H).
Example 331 ##STR00386## 1-tert- butyl-3-[4- (7-methoxy- 1-methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-urea Mass
(M + H.sup.+): 400.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.15
(s, 9H), 1.39 (m, 2H), 1.60 (m, 2H), 2.94 (m, 2H), 2.96 (s, 3H),
3.80 (s, 3H), 5.49 (s, 1H), 5.57 (t, 1H), 6.84 (d, 1H), 7.06 (d,
1H), 7.94 (d, 1H), 8.10 (t, 1H). Example 332 ##STR00387## [4-(7-
methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid cyclo- pentylester Mass (M +
H.sup.+): 413.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.44~ 1.55
(m, 8H), 1.62 (m, 2H), 1.73 (m, 2H), 2.95 (s, 3H), 2.99 (m, 2H),
3.50 (q, 2H), 3.80 (s, 3H), 4.89 (m, 1H), 6.85 (d, 1H), 6.95 (t,
1H), 7.06 (s, 1H), 7.95 (d, 1H), 8.08 (t, 1H). Example 333
##STR00388## [4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid phenylester Mass
(M + H.sup.+): 421.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.54
(m, 2H), 1.69 (m, 2H), 2.95 (s, 3H), 3.09 (q, 2H), 3.53 (m, 2H),
3.80 (s, 3H), 6.85 (d, 1H), 7.06 (m, 3H), 7.14 (t, 1H), 7.30 (t,
2H), 7.71 (t, 1H), 7.95 (d, 1H), 8.12 (t, 1H). Example 334
##STR00389## 3-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-1,1- dimethyl-urea Mass (M +
H.sup.+): 372.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.45 (m,
2H), 1.61 (m, 2H), 2.71 (s, 6H), 2.94 (s, 3H), 3.01 (q, 2H), 3.52
(q, 2H), 3.80 (s, 3H), 6.19 (t, 1H), 6.84 (dd, 1H), 7.04 (s, 1H),
7.93 (d, 1H), 8.06 (t, 1H). Example 335 ##STR00390## 1-cyclohexyl-
3-[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-urea Mass (M + H.sup.+): 426.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.01 (m, 2H), 1.08 (m, 1H), 1.18 (m, 2H),
1.40 (m, 2H), 1.49 (m, 1H), 1.60 (m, 4H), 1.69 (m, 2H), 2.95 (s,
3H), 2.99 (m, 2H), 3.31 (m, 1H), 3.50 (q, 2H), 3.81 (s, 3H), 5.60
(d, 1H), 5.65 (t, 1H), 6.85 (d, 1H), 7.07 (s, 1H), 7.95 (s, 1H),
8.08 (t, 1H). Example 336 ##STR00391## [4-(7- methoxy-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
thiocarbamic acid-S- Mass (M + H.sup.+): 403.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.19 (d, 6H), 1.47 (m, 2H), 1.61 (m, 2H),
2.95 (s, 3H), 3.10 (m, 2H), 3.39 (m, 1H), 3.50 (q, 2H), 3.81 (s,
3H), 6.86 (d, 1H), 7.08 (t, 1H), 7.95 (s, 1H), 7.96 (d, isopropyl
ester 1H), 8.21 (t, 1H). Example 337 ##STR00392## 1-isopropyl-3-
[4-(7- methoxy-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- thiourea Mass (M + H.sup.+): 402.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.04 (d, 6H), 1.53 (m, 2H), 1.63 (m,
2H), 3.02 (s, 3H), 3.45 (br, 2H), 3.52 (q, 2H), 3.80 (s, 3H), 6.85
(dd, 1H), 7.07 (dd, 2H), 7.20 (br, 1H), 7.95 (d, 1H), 8.11 (t, 1H).
Example 338 ##STR00393## N-[4-(7- methoxy-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- methanesul- fonamide
Mass (M + H.sup.+): 379.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.53 (m, 2H), 1.67 (m, 2H), 2.84 (s, 3H), 2.95 (s, 3H), 2.96
(q, 2H), 3.52 (q, 2H), 3.80 (s, 3H), 6.84 (d, 1H), 6.90 (t, 1H),
7.05 (s, 1H), 7.93 (d, 1H), 8.10 (t, 1H).
<Example 339> Preparation of
N-{4-[7-methoxy-1-methyl-8-(4-nitro-benzyl)-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-3-methyl-butyramide
##STR00394##
[1337]
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-3-methyl-butyramide (100 mg, 0.26 mmol) prepared in
Example 285 was dissolved in 2 ml of dichloromethane, to which
silvertrifluoromethanesulfonate (67 mg, 0.26 mmol) and
4-nitrobenzylbromide were added, followed by reaction at room
temperature for 18 hours. Upon completion of the reaction, the
precipitate was filtered. The filtrate was distilled under reduced
pressure. The concentrate was separated and purified by column
chromatography. As a result, 78 mg of a target compound was
obtained (58% yield).
[1338] Mass (M+H.sup.+): 520.0
[1339] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.40 (m,
2H), 1.61 (m, 2H), 1.87 (d, 2H), 1.90 (m, 1H), 3.00 (q, 2H), 3.36
(s, 3H), 3.50 (q, 2H), 3.76 (s, 2H), 3.86 (s, 3H), 6.50 (d, 1H),
7.17 (t, 1H), 7.48 (dd, 2H), 7.68 (d, 1H), 8.19 (t, 1H), 8.23 (dd,
2H).
<Example 340> Preparation of
N-[4-(7-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-but-
yl]-3-methyl-butyramide
##STR00395##
[1341]
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-3-methyl-butyramide (0.1 g, 0.26 mmol) prepared in
Example 285 and aluminum chloride (AlCl.sub.3) were dissolved in
toluene solvent, followed by reflux stirring for 3 hours. Upon
completion of the reaction, ph of the reactant was adjusted to 8 at
room temperature. The reactant was extracted with ethylacetate and
water. The extract was dried over magnesium sulfate, and then
distilled under reduced pressure. As a result, 0.7 g of a target
compound was obtained (73% yield).
[1342] Mass (M+H.sup.+): 371.2
[1343] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.44 (m,
2H), 1.62 (m, 2H), 1.87 (m, 3H), 2.93 (s, 3H), 3.04 (q, 2H), 3.48
(q, 2H), 6.70 (d, 1H), 6.90 (s, 1H), 7.70 (s, 1H), 7.86 (d, 1H),
7.98 (s, 1H), 9.64 (s, 1H).
<Example 341> Preparation of
N-{4-[7-(4-cyano-benzyloxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-3-methyl-butyramide
##STR00396##
[1345]
N-[4-(7-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-3-methyl-butyramide (0.3 g, 0.79 mmol) prepared in
Example 340, alpha-bromo-P-tolunitrile (0.31 g, 2 eq) and
cesiumcarbonate (1.28 g, 5 eq) were dissolved in NMP solvent,
followed by reflux stirring at 100.degree. C. for 2 hours. Upon
completion of the reaction, the resulting solid was filtered and as
a result, 0.11 g of a target compound was obtained (29% yield).
[1346] Mass (M+H.sup.+): 486.2
[1347] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.78 (d, 6H), 1.44 (m,
2H), 1.61 (m, 2H), 1.87 (m, 3H), 2.95 (s, 3H), 3.04 (q, 2H), 3.50
(q, 2H), 5.30 (d, 2H), 5.86 (s, 1H), 6.93 (d, 1H), 7.15 (s, 1H),
7.63 (d, 2H), 7.70 (m, 1H), 7.84 (d, 2H), 7.85 (d, 1H), 8.20 (s,
1H).
[1348] The compounds shown in Table 22 below were prepared by the
same manner as described in Example 341.
TABLE-US-00022 TABLE 22 Example Structure Name Data Example 342
##STR00397## N-{4-[7-(3- cyano- propoxy)-1- methyl- [1,2,4]triaz-
olo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3- methyl- Mass (M +
H.sup.+): 438.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
6H), 1.44 (m, 2H), 1.63 (m, 2H), 1.87 (m, 3H), 2.02 (m, 2H), 2.65
(t, 2H), 2.95 (s, butyramide 3H), 3.13 (q, 2H), 3.50 (d, 2H), 4.09
(d, 2H), 6.85 (d, 1H), 7.07 (s, 1H), 7.70 (m, 1H), 7.95 (d, 1H),
8.10 (m, 1H). Example 343 ##STR00398## 3-methyl-N- {4-[1- methyl-7-
(tetrahydro- pyran-2-yl- methoxy)- [1,2,4]triaz- olo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+): 469.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.30 (m, 1H),
1.46 (m, 5H), 1.61 (m, 3H), 1.80 (m, 1H), 1.86 (m, 3H), 2.94 (s,
3H), 3.04 (m, butyramide 2H), 3.37 (m, 1H), 3.49 (m, 2H), 3.60 (m,
1H), 3.86 (m, 1H), 3.96 (d, 2H), 6.84 (d, 1H), 7.03 (s, 1H), 7.69
(t, 1H), 7.92 (d, 1H), 8.08 (t, 1H). Example 344 ##STR00399##
3-methyl-N- {4-[1- methyl-7- (tetrahydro- pyran-4- yloxy)-
[1,2,4]triaz- olo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 455.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d,
6H), 1.44 (s, 2H), 1.62 (m, 4H), 1.87 (s, 3H), 1.97 (d, 2H), 2.94
(s, 3H), 3.04 (s, butyl}- 2H), 3.47 (m, butyramide 4H), 3.84 (d,
2H), 4.69 (s, 1H), 6.87 (d, 1H), 7.11 (s, 1H), 7.71 (s, 1H), 7.94
(d, 1H), 8.01 (s, 1H). Example 345 ##STR00400## 4-{1-methyl-
4-[4-(3- methyl- butylamino)- butylamino]- [1,2,4]triaz- olo[4,3-
a]quinoxaline- 7-yloxy}- Mass (M + H.sup.+): 554.3; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.78 (d, 9H), 1.36 (s, 6H), 1.44 (m,
4H), 1.45 (m, 2H), 1.60 (m, 2H), 1.87 (m, piperidine- 7H), 2.93 (s,
1-carboxylic 3H), 2.95 (s, acid-tert- 2H), 3.63 (m, butylester 2H),
6.88 (s, 1H), 7.11 (s, 1H), 7.69 (s, 1H), 7.92 (t, 1H), 8.11 (s,
1H). Example 346 ##STR00401## N-[4-(7- benzyloxy-1- methyl-
[1,2,4]triaz- olo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3- methyl-
butyramide Mass (M + H.sup.+): 461.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.77 (d, 6H), 1.44 (m, 2H), 1.64 (m, 2H), 1.87 (m,
3H), 2.94 (s, 3H), 3.04 (q, 2H), 3.51 (q, 2H), 5.17 (s, 2H), 6.90
(d, 2H), 7.14 (s, 1H), 7.30 (m, 1H), 7.37 (m, 2H), 7.44 (m, 2H),
7.70 (t, 1H), 7.93 (d, 1H), 8.10 (s, 1H).
<Example 347> Preparation of
N-(4-{7-[4-(N-hydroxycarbaimidolyl)-benzoyl]-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino}-butyl)-3-methyl-butyramide
##STR00402##
[1350]
N-{4-[7-(4-Cyano-benzyloxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxal-
ine-4-ylamino]-butyl}-3-methyl-butyramide (0.04 g, 0.08 mmol)
prepared in Example 341, potassium-tert-butoxide (0.03 mg, 3.5 eq)
and hydroxylamine hydrochloride (0.03 mg, 4.5 eq) were dissolved in
dimethylformamide, followed by stirring at room temperature for 2
days. Upon completion of the reaction, the reaction mixture was
extracted with ethylacetate and water. The organic layer was dried
over magnesium sulfate to eliminate moisture, followed by
distillation and drying under reduced pressure. As a result, 0.03 g
of a target compound was obtained (47% yield).
[1351] Mass (M+H.sup.+): 519.3
[1352] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.44 (m,
2H), 1.63 (m, 2H), 1.87 (m, 3H), 2.95 (s, 3H), 3.04 (q, 2H), 3.50
(q, 2H), 5.20 (d, 2H), 5.86 (s, 1H), 6.93 (d, 1H), 7.15 (s, 1H),
7.43 (d, 2H), 7.66 (d, 2H), 7.67 (m, 1H), 7.95 (d, 1H), 8.10 (m,
1H), 9.63 (s, 1H).
[1353] The compounds shown in Table 23 below were prepared by using
the compound prepared by the same manner as described in Example
341 as an intermediate.
TABLE-US-00023 TABLE 23 Exam- ple Structure Name Data Exam- ple 348
##STR00403## 3-methyl-N- (4-{1- methyl-7- [4-(2H- tetrazol-5- yl)-
benzyloxy]- [1,2,4]triaz- olo[4,3- a]quinox- aline-4- ylamino}-
butyl)- butyramide Mass (M + H.sup.+): 529.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 1.45 (s, 2H), 1.62 (m, 4H), 1.88 (s,
3H), 2.95 (s, 3H), 3.06 (m, 2H), 3.53 (s, 2H), 5.29 (s, 2H), 6.96
(d, 1H), 7.20 (m, 1H), 7.65 (d, 2H), 7.80 (s, 1H), 7.96 (d, 1H),
8.15 (d, 1H) . Exam- ple 349 ##STR00404## 3-methyl- N-(4-{1-
methyl-7- [4-(2- methyl-2H- tetrazolo- 5-yl)- benzyloxy]-
[1,2,4]triaz- olo[4,3- a]quinox- aline-4- Mass (M + H.sup.+):
543.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.46
(s, 2H), 1.63 (m, 2H), 1.87 (m, 3H), 2.95 (s, 3H), 3.04 (m, 2H),
3.50 (m, 2H), 4.39 (s, 3H), 5.28 (s, 2H), 6.96 (d, 1H), 7.18
ylamino}- (d, 2H), 7.62 (m, butyl)- 2H), 7.70 (m, 1H), butyramide
7.96 (d, 1H), 8.05 (d, 2H), 8.06 (s, 1H).
<Example 350> Preparation of benzoic acid
1-methyl-4-[4-(3-methyl-butylamino)-butylamino]-[1,2,4]triazolo[4,3-a]qui-
noxaline-7-yl ester
##STR00405##
[1355]
N-[4-(7-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-3-methyl-butyramide (0.2 g, 0.54 mmol) prepared in
Example 340, triethylamine (0.37 ml, 10 eq) and benzoylchloride
(0.14 g, 1.1 eq) were dissolved in dichloromethane, followed by
stirring at room temperature for 2 days. The reaction was
terminated by adding methanol, followed by distillation under
reduced pressure. The reactant was purified by column
chromatography. As a result, 0.12 g of a target compound was
obtained (93% yield).
[1356] Mass (M+H.sup.+): 475.2
[1357] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.77 (t, 6H), 1.44
(m, 2H), 1.64 (m, 2H), 1.87 (m, 3H), 3.00 (s, 3H), 3.04 (q, 2H),
3.50 (q, 2H), 7.20 (d, 2H), 7.46 (s, 1H), 7.60 (m, 2H), 7.73 (m,
2H), 8.13 (m, 3H), 8.30 (s, 1H).
[1358] The compounds shown in Table 24 below were prepared by the
same manner as described in Example 350.
TABLE-US-00024 TABLE 24 Example Structure Name Data Example 351
##STR00406## morpholine- 4-carboxylic acid-1- methyl-4-[4-
(3-methyl- butylamino)- butylamino]- [1,2,4]triaz- olo[4,3-
a]quinoxaline- Mass (M + H.sup.+): 484.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 1.44 (m, 2H), 1.62 (m, 2H), 1.87 (m,
3H), 2.98 (s, 3H), 3.04 (q, 2H), 3.40 7-yl-ester (s, 2H), 3.49 (m,
2H), 3.60 (s, 2H), 3.63 (s, 4H), 7.03 (d, 1H), 7.30 (s, 1H), 7.69
(t, 1H), 8.02 (d, 1H), 8.21 (t, 1H). Example 352 ##STR00407##
3-methyl- thiophene-2- carboxylic acid-1- methyl-4-[4- (3-methyl-
butylamino)- butylamino]- [1,2,4]tri- azolo[4,3- Mass (M +
H.sup.+): 495.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.78 (d,
6H), 1.44 (m, 2H), 1.62 (m, 2H), 1.87 (m, 3H), 2.53 (s, 3H), 3.00
(s, 3H), 3.05 a]quinoxaline- (q, 2H), 3.51 7-yl-ester (q, 2H), 7.13
(m, 2H), 7.40 (s, 1H), 7.69 (s, 1H), 7.91 (d, 1H), 8.09 (d, 1H),
8.27 (t, 1H). Example 353 ##STR00408## dimethyl- thiocarbamic
acid-O-{1- methyl-4-[4- (3-methyl- butylamino)- butylamino]-
[1,2,4]triaz- olo[4,3- a]quinoxaline- Mass (M + H.sup.+): 458.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44 (m, 2H),
1.62 (m, 2H), 1.87 (m, 3H), 2.99 (s, 3H), 3.05 (m, 2H), 3.32
7-yl}-ester (s, 3H), 3.35 (s, 3H), 6.97 (d, 1H), 7.20 (s, 1H), 7.69
(s, 1H), 8.04 (d, 1H), 8.26 (s, 1H).
<Preparative Example 21> Preparation of
[4-(3-hydrazino-7-methylsulfanyl-3,4-dihydro-quinoxaline-2-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00409##
[1359] Step 1: Preparation of
[4-(3-chloro-7-methylsulfanyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1360] 1.3 g of a target compound was obtained (89% yield) by the
same manner as described in Example 57, except that
2,3-dichloro-6-methylsulfanyl-quinoxaline (0.9 g, 3.67 mmol) was
used.
[1361] Mass (M+H.sup.+): 397.2
[1362] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.42
(m, 2H), 1.57 (m, 2H), 2.54 (s, 3H), 2.92 (m, 2H), 3.42 (q, 2H),
6.73 (t, 1H), 7.18 (dd, 1H), 7.29 (d, 1H), 7.42 (t, 1H), 7.56 (d,
1H).
Step 2: Preparation of
[4-(3-hydrazino-7-methylsulfanyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1363]
[4-(3-Chloro-7-methylsulfanyl-quinoxaline-2-ylamino)-butyl]-carbami-
c acid-tert-butylester (1.3 g, 3.28 mmol) prepared in step 1 of
Preparative Example 21 and hydrazine hydrate (4.77 ml, 98 mmol)
were dissolved in 15 ml of dioxane, followed by reflux stirring for
5 hours. Upon completion of the reaction, the reaction mixture was
extracted with ethylacetate and water. The extract was dried over
magnesium sulfate to eliminate moisture, followed by filtering,
distillation and drying under reduced pressure. As a result, 1.29 g
of a target compound (100% yield) was obtained, which proceeded to
the next reaction without purification.
[1364] Mass (M+H.sup.+): 393.2
<Example 354> Preparation of
[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester
##STR00410##
[1366] 1.1 g of a target compound was obtained (80% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(3-hydrazino-7-methylsulfanyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (1.29 g, 3.29 mmol) prepared in step 2 of
Preparative Example 21 was used.
[1367] Mass (M+H.sup.+): 417.2
[1368] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.61 (m, 2H), 2.52 (s, 3H), 2.93 (q, 2H), 2.96 (s, 3H), 3.49
(q, 2H), 6.75 (t, 1H), 7.13 (d, 1H), 7.36 (s, 1H), 7.96 (d, 1H),
8.15 (t, 1H).
<Example 355> Preparation of
N.sup.1-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid
##STR00411##
[1370] 1.13 g of a target compound was obtained (86% yield) by the
same manner as described in Example 58, except that
[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester (1 g, 2.4 mmol) prepared in
Example 354 was used.
[1371] Mass (M+H.sup.+): 317.2
[1372] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.60 (m, 2H), 1.69 (m,
2H), 2.52 (s, 3H), 2.82 (q, 2H), 2.97 (s, 3H), 3.54 (q, 2H), 7.15
(d, 1H), 7.36 (s, 1H), 7.69 (br, 2H), 7.98 (d, 1H), 8.33 (t,
1H).
<Example 356> Preparation of
3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide
##STR00412##
[1374] 0.35 g of a target compound was obtained (95% yield) by the
same manner as described in Example 37, except that
N.sup.1-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid (0.5 g, 0.92 mmol)
prepared in Example 355 was used.
[1375] Mass (M+H.sup.+): 401.2
[1376] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45
(m, 2H), 1.62 (m, 2H), 1.87 (m, 2H), 1.90 (m, 1H), 2.46 (s, 3H),
2.96 (s, 3H), 3.03 (q, 2H), 3.50 (q, 2H), 7.14 (d, 1H), 7.35 (s,
1H), 7.70 (t, 1H), 7.96 (s, 1H), 8.16 (t, 1H).
<Example 357> Preparation of
2-(S)-fluoro-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino)-butyl]-butyramide
##STR00413##
[1378] 63 mg of a target compound was obtained (42% yield) by the
same manner as described in Example 356.
[1379] Mass (M+H.sup.+): 419.1
[1380] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 3H), 0.89
(d, 3H), 1.49 (m, 2H), 1.62 (m, 2H), 2.10 (m, 1H), 2.52 (s, 3H),
2.96 (s, 3H), 3.16 (m, 2H), 3.50 (q, 2H), 4.61 (d, 1H), 7.13 (d,
1H), 7.35 (s, 1H), 7.96 (d, 1H), 8.07 (t, 1H), 8.18 (t, 1H).
<Example 358> Preparation of
2-(S)-hydroxy-3-methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,-
3-a]quinoxaline-4-ylamino)-butyl]-butyramide
##STR00414##
[1382] 70 mg of a target compound was obtained (68% yield) by the
same manner as described in Example 39, except that
N1-(1-methyl-(7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid (0.14 g, 0.25 mmol)
prepared in Example 355 was used.
[1383] Mass (M+H.sup.+): 417.2
<Example 359> Preparation of
N-[4-(7-methanesulfinyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide
##STR00415##
[1385]
3-Methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide (100 mg, 0.25 mmol) prepared
in Example 356 was dissolved in a mixed solution comprising 5 ml of
dichloromethane and 2 ml of methanol, to which m-CPBA (120 mg, 0.5
mmol) was slowly added, followed by reaction at room temperature
for 18 hours. Upon completion of the reaction, the solvent was
concentrated under reduced pressure, followed by column
chromatography for separation and purification. As a result, 70 mg
of a target compound (70% yield) was obtained.
[1386] Mass (M+H.sup.+): 417.2
[1387] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.78 (d, 6H), 1.44
(m, 2H), 1.63 (m, 2H), 1.87 (m, 2H), 1.90 (m, 1H), 2.77 (s, 3H),
3.00 (s, 3H), 3.03 (q, 2H), 3.51 (q, 2H), 7.53 (d, 1H), 7.72 (t,
1H), 7.80 (s, 1H), 8.23 (d, 1H), 8.36 (t, 1H)
<Example 360> Preparation of
N-[4-(7-methanesulfonyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide
##STR00416##
[1389]
3-Methyl-N-[4-(1-methyl-7-methylsulfanyl-[1,2,4]triazolo[4,3-a]quin-
oxaline-4-ylamino)-butyl]-butyramide (100 mg, 0.25 mmol) prepared
in Example 356 was dissolved in a mixture comprising 5 ml of
dichloromethane and 2 ml of methanol, to which m-CPBA (240 mg, 1
mmol) was slowly added, followed by reaction at room temperature
for 24 hours. Upon completion of the reaction, the solvent was
concentrated under reduced pressure, followed by column
chromatography for separation and purification. As a result, 67 mg
of a target compound (61% yield) was obtained.
[1390] Mass (M+H.sup.+): 433.2
[1391] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44
(m, 2H), 1.63 (m, 2H), 1.87 (m, 2H), 1.90 (m, 1H), 3.01 (s, 3H),
3.06 (q, 2H), 3.26 (s, 3H), 3.53 (q, 2H), 7.72 (m, 2H), 7.99 (s,
1H), 8.27 (d, 1H), 8.49 (t, 1H)
<Preparative Example 22> Preparation of
[4-(7-fluoro-3-hydrazino-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00417##
[1392] Step 1: Preparation of
[4-(3-chloro-7-fluoro-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1393] A target compound was obtained (64% yield) by the same
manner as described in Example 57, except that
2,3-dichloro-6-fluoroquinoxaline (0.50 g, 2.30 mmol) was used. The
following reaction was carried out without purification.
[1394] Mass (M+H.sup.+): 369.1
[1395] .sup.1H NMR (300 MHz, CDCl.sub.3): .delta.1.47 (s, 9H),
1.62-1.67 (m, 2H), 1.74-1.80 (m, 2H), 3.20-3.25 (m, 2H), 3.60-3.65
(m, 2H), 4.80 (brs, 1H), 5.73 (brs, 1H), 7.12-7.16 (m, 1H),
7.35-7.38 (m, 1H), 7.75-7.78 (m, 1H).
Step 2: Preparation of
[4-(7-fluoro-3-hydrazino-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1396] A target compound was obtained (2 steps, 46% yield) by the
same manner as described in step 2 of Preparative Example 20,
except that
[4-(3-chloro-7-fluoro-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (2 g, 9.21 mmol) prepared in step 1 of
Preparative Example 22 was used.
[1397] Mass (M+H.sup.+): 365.2
<Example 361> Preparation of
[4-(7-fluoro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester
##STR00418##
[1399] A target compound was obtained (2 steps, 54% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(7-fluoro-3-hydrazino-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester prepared in step 2 of Preparative Example 22
was used.
[1400] Mass (M+H.sup.+): 388.4
[1401] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.36-1.50 (m, 2H), 1.60-1.68 (m, 2H), 2.93-3.00 (m, 2H), 3.02 (s,
3H), 3.50-3.57 (m, 2H), 6.79 (t, J=5.07 Hz, 1H), 7.11-7.17 (m, 1H),
7.33-7.38 (m, 1H), 8.08-8.13 (m, 1H), 8.35 (t, J=5.67 Hz, 1H).
<Example 362> Preparation of
4-(7-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-carbami-
c acid-tert-butylester
##STR00419##
[1403] A target compound was obtained by the same manner as
described in Example 361, except that 2,3,6-trichloro-quinoxaline
was used instead of 2,3-dichloro-6-fluoroquinoxaline.
[1404] Mass (M+H.sup.+): 405.1
[1405] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.41-1.51 (m, 2H), 1.60-1.68 (m, 2H), 2.93-2.97 (m, 2H), 3.00 (s,
3H), 3.51-3.57 (m, 2H), 6.79 (brs, 1H), 7.30 (dd, J=8.88 Hz, 1H),
7.59 (d, J=2.34 Hz, 1H), 8.08 (d, J=8.88 Hz, 1H), 8.37 (t, J=5.61
Hz, 1H).
<Preparative Example 23> Preparation of
{4-[3-hydrazino-7-(2-methoxy-ethoxy)-quinoxaline-2-ylamino]-butyl}-carbam-
ic acid-tert-butylester
##STR00420##
[1406] Step 1: Preparation of
2,3-dichloro-6-(2-methoxy-ethoxy)-quinoxaline
[1407] 1.6 g of a target compound was obtained (73% yield) by the
same manner as described in step 1 of Preparative Example 5, except
that 6-(2-methoxy-ethoxy)-1,4-dihydro-quinoxaline-2,3-dione (1.9 g,
8.0 mmol) was used.
[1408] Mass (M+H.sup.+): 273.0
[1409] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.29 (s 3H), 3.70 (t,
2H), 4.28 (t, 2H), 7.47 (s, 1H), 7.56 (dd, 1H), 7.95 (d, 1H)
Step 2: Preparation of
{4-[3-chloro-7-(2-methoxy-ethoxy)-quinoxaline-2-ylamino]-butyl}-carbamic
acid-tert-butylester
[1410] 632 mg of a target compound was obtained (81% yield) by the
same manner as described in Example 57, except that
2,3-dichloro-6-(2-methoxy-ethoxy)-quinoxaline (500 mg, 1.83 mmol)
prepared in step 1 of Preparative Example 23 was used.
[1411] Mass (M+H.sup.+): 425.1
[1412] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.40
(m, 2H), 1.57 (m, 2H), 2.91 (q, 2H), 3.28 (s, 3H), 3.41 (q, 2H),
3.66 (m, 2H), 4.18 (m, 2H), 6.74 (t, 1H), 6.96 (s, 1H), 6.99 (d,
2H), 7.33 (t, 1H), 7.57 (d, 1H).
Step 3: Preparation of
{4-[3-hydrazino-7-(2-methoxy-ethoxy)-quinoxaline-2-ylamino]-butyl}-carbam-
ic acid-tert-butylester
[1413] 2.3 g of a target compound was obtained (72% yield) by the
same manner as described in step 2 of Preparative Example 20,
except that
{4-[3-chloro-7-(2-methoxy-ethoxy)-quinoxaline-2-ylamino]-butyl}-carbamic
acid-tert-butylester (3.3 g, 7.8 mmol) prepared in step 2 of
Preparative Example 23 and hydrazine hydrate (7.5 ml, 155 mmol)
were used.
[1414] Mass (M+H.sup.+): 421.2
<Example 363> Preparation of
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-tert-butylester
##STR00421##
[1416] 1.05 g of a target compound was obtained (47% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
{4-[3-hydrazino-7-(2-methoxy-ethoxy)-quinoxaline-2-ylamino]-butyl}-carbam-
ic acid-tert-butylester (2.1 g, 5.0 mmol) prepared in step 3 of
Preparative Example 23 was used.
[1417] Mass (M+H.sup.+): 445.2
[1418] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.60 (m, 2H), 2.92 (q, 2H), 2.94 (s, 3H), 3.29 (s, 3H), 3.50
(m, 2H), 3.65 (t, 2H), 4.15 (t, 2H), 6.76 (t, 1H), 6.84 (dd, 1H),
7.06 (d, 1H), 7.94 (d, 1H), 8.08 (brm, 1H).
<Example 364> Preparation of
N.sup.1-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00422##
[1420] 1 g of a target compound was obtained (86% yield) by the
same manner as described in Example 58, except that
{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino]-butyl}-carbamic acid-tert-butylester (0.9 g, 2.02 mmol)
prepared in Example 363 was used.
[1421] Mass (M+H.sup.+): 345.2
[1422] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.59 (m, 2H), 1.68 (m,
2H), 2.83 (m, 2H), 2.96 (s, 3H), 3.29 (s, 3H), 3.53 (m, 2H), 3.66
(t, 2H), 4.15 (t, 2H), 6.89 (dd, 1H), 7.06 (s, 1H), 7.62 (brs, 2H),
7.97 (d, 1H), 8.18 (t, 1H).
<Example 365> Preparation of
N-{4-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-y-
lamino]-butyl}-3-methyl-butyramide
##STR00423##
[1424] 60 mg of a target compound was obtained (67% yield) by the
same manner as described in Example 37, except that
N.sup.1-[7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl]-butane-1,4-diamine ditrifluoroacetic acid (120 mg, 0.21 mmol)
prepared in Example 364 and isovalerylchloride (0.03 ml, 0.23 mmol)
were used.
[1425] Mass (M+H.sup.+): 429.2
[1426] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45
(m, 2H), 1.62 (m, 2H), 1.86 (d, 2H), 1.88 (m, 1H), 2.95 (s, 3H),
3.04 (q, 2H), 3.27 (s, 3H), 3.50 (q, 2H), 3.65 (t, 1H), 4.15 (t,
2H), 6.86 (dd, 1H), 7.05 (s, 1H), 7.69 (t, 1H), 7.95 (d, 1H), 8.09
(t, 1H).
[1427] The compounds shown in Table 25 below were prepared by the
same manner as described in Example 365.
TABLE-US-00025 TABLE 25 Example Structure Name Data Example 366
##STR00424## {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]triaz-
olo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic acid Mass (M +
H.sup.+): 431.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.10 (d,
6H), 1.45 (m, 2H), 1.60 (m, 2H), 2.95 (s, 3H), 2.99 (m, 2H), 3.27
(s, 3H), 3.50 (m, 2H), 3.64 (t, 2H), 4.15 (t, 2H), isopropylester
4.18 (m, 1H), 6.86 (d, 1H), 6.94 (t, 1H), 7.06 (s, 1H), 7.95 (d,
1H), 8.08 (t, 1H), 7.06 (s, 1H), 7.95 (d, 1H), 8.08 (t, 1H).
Example 367 ##STR00425## {4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic
acid Mass (M + H.sup.+): 431.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.0.83 (t, 3H), 1.50 (m, 4H), 1.66 (m, 2H), 2.95 (s, 3H), 3.02
(q, 2H), 3.31 (s, 3H), 3.53 (q, 2H), 3.67 (t, 2H), 3.85 propylester
(t, 2H), 4.17 (t, 2H), 6.79 (brm, 1H), 6.87 (d, 1H), 7.09 (s, 1H),
7.82 (m, 1H), 7.95 (d, 1H). Example 368 ##STR00426## {4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- carbamic Mass (M + H.sup.+): 445.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta..78 (t, 3H), 1.07 (d, 3H), 1.42 (m,
2H), 1.45 (m, 2H), 1.63 (m, 2H), 2.95 (s, 3H), 2.97 (m, 2H), 3.29
(s, 3H), 3.45 acid-sec- (q, 2H), 3.66 (t, butylester 2H), 4.15 (t,
2H), 4.53 (m, 1H), 6.89 (dd, 1H), 6.91 (t, 1H), 6.99 (t, 1H), 7.19
(s, 1H), 7.96 (d, 1H). Example 369 ##STR00427## {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- carbamic acid Mass (M + H.sup.+): 445.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.81 (d, 1H), 1.45 (m, 2H),
1.62 (m, 2H), 1.76 (m, 1H), 2.95 (s, 3H), 2.99 (q, 2H), 3.28 (s,
3H), 3.59 (q, 2H), 3.66 isobutylester (m, 4H), 4.15 (t, 2H), 6.86
(dd, 1H), 7.03 (t, 1H), 7.07 (s, 1H), 7.95 (d, 1H), 8.09 (t, 1H).
Example 370 ##STR00428## {4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic
acid Mass (M + H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.1.46 (m, 2H), 1.62 (m, 2H), 2.95 (s, 3H), 3.00 (q, 2H), 3.29
(s, 3H), 3.50 (q, 2H), 3.66 (t, 2H), 4.15 (t, 2H), 4.41 allylester
(d, 2H), 5.10 (d, 1H), 5.23 (d, 1H), 5.84 (m, 1H), 6.87 (d, 1H),
7.06 (s, 1H), 7.16 (t, 1H), 7.95 (d, 1H), 8.11 (t, 1H). Example 371
##STR00429## {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic acid
cyclopentyl- Mass (M + H.sup.+): 457.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.43 (m, 2H), 1.45 (m, 2H), 1.48 (m, 2H), 1.60 (m, 2H),
2.95 (s, 3H), 2.97 (m, 2H), 3.28 (s, 3H), 3.38 (m, 4H), 3.50 (m,
2H), 3.66 (t, ester 2H), 4.15 (t, 2H), 4.88 (m, 1H), 6.86 (dd, 1H),
6.97 (t, 1H), 7.07 (d, 1H), 7.94 (d, 1H), 8.14 (t, 1H). Example 372
##STR00430## {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic acid
phenylester Mass (M + H.sup.+): 467.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.54 (m, 2H), 1.68 (m, 2H), 2.95 (s, 3H), 3.09 (m, 2H),
3.29 (s, 3H), 3.53 (m, 2H), 3.64 (t, 2H), 4.14 (t, 1H), 6.86 (dd,
1H), 7.03 (m, 2H), 7.07 (d, 1H), 7.15 (t, 1H), 7.32 (m, 2H), 7.72
(t, 1H), 7.93 (d, 1H), 8.12 (t, 1H). Example 373 ##STR00431##
{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+): 479.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.1.47 (m, 2H), 1.62 (m, 2H),
2.95 (s, 3H), 3.02 (q, 2H), 3.28, (s, 3H), 3.50 (q, 2H), 3.65 (t,
2H), carbamic acid 4.14 (t, 2H), 4.95 benzylester (s, 2H), 6.87 (d,
1H), 7.07 (s, 1H), 7.25 (t, 1H), 7.30 (m, 5H), 7.96 (d, 1H), 8.11
(t, 1H). Example 374 ##STR00432## {4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
acetamide Mass (M + H.sup.+): 387.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.43 (m, 2H), 1.62 (m, 2H), 1.74 (s, 3H), 2.94 (s, 3H),
3.02 (m, 2H), 3.28 (s, 3H), 3.50 (q, 2H), 3.65 (brm, 2H), 4.15
(brm, 2H), 6.86 (d, 1H), 7.06 (s, 1H), 7.76 (brm, 1H), 7.94 (d,
1H), 8.09 (t, 1H). Example 375 ##STR00433## {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-2,2- dimethyl- Mass (M + H.sup.+): 429.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.1.03 (s, 9H), 1.46 (q, 2H),
1.60 (q, 2H), 2.95 (s, 3H), 3.05 (m, 2H), 3.29 (s, 3H), 3.49 (q,
2H), 3.65 (t, 2H), 4.15 propionamide (t, 2H), 6.86 (d, 1H), 7.06
(s, 1H), 7.38 (t, 1H), 7.95 (d, 1H), 8.10 (t, 1H). Example 376
##STR00434## {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- isobutyramide Mass (M
+ H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.92 (d,
6H), 1.43 (m, 2H), 1.62 (m, 2H), 2.27 (m, 1H), 2.95 (s, 3H), 3.02
(q, 2H), 3.29 (s, 3H), 3.50 (q, 2H), 3.66 (t, 2H), 4.15 (t, 2H),
6.84 (d, 1H), 7.06 (s, 1H), 7.66 (t, 1H), 7.94 (d, 1H), 8.10 (t,
1H). Example 377 ##STR00435## cyclopropane carboxylic acid-{4-[7-
(2-methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- Mass (M + H.sup.+): 413.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.55 (m, 6H), 0.59 (m, 2H), 1.45 (m,
2H), 1.63 (m, 2H), 2.95 (s, 3H), 3.05 (m, 1H), 3.06 (q, 2H), 3.29
(s, 3H), 3.50 butyl}-amide (q, 2H), 3.65 (q, 2H), 4.15 (q, 2H),
6.86 (d, 1H), 7.06 (d, 1H), 7.94 (s, 1H), 7.98 (t, 1H), 8.11 (t,
1H). Example 378 ##STR00436## 3-methyl- butene-2-oic acid-{4-[7-
(2-methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- Mass (M + H.sup.+): 427.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.1.46 (m, 2H), 1.63 (m, 3H), 1.71 (s,
3H), 2.01 (s, 3H), 2.95 (s, 3H), 3.06 (q, 2H), 3.29 (s, 3H), 3.50
(q, 2H), 3.66 butyl}-amide (t, 2H), 4.15 (t, 2H), 5.57 (s, 1H),
6.87 (d, 1H), 7.06 (s, 1H), 7.66 (t, 1H), 7.96 (d, 1H), 8.10 (t,
1H). Example 379 ##STR00437## butene-2-oic acid{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-amide Mass (M + H.sup.+): 413.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.1.50 (m, 2H), 1.66 (m, 2H), 1.74 (d,
2H), 2.95 (s, 3H), 3.10 (q, 2H), 3.13 (s, 3H), 3.45 (q, 2H), 3.67
(t, 2H), 4.17 (t, 2H), 5.86 (d, 1H), 6.55 (m, 1H), 6.88 (d, 1H),
7.08 (s, 1H), 7.63 (t, 1H), 7.85 (t, 1H), 7.96 (d, 1H). Example 380
##STR00438## N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-2- methyl- Mass (M +
H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.73 (t,
3H), 1.91 (d, 3H), 1.20 (m, 1H), 1.46 (m, 3H), 1.62, (m, 2H), 2.05
(m, 1H), 2.94 (s, 3H), 3.07 (m, 2H), 3.49, butyramide (q, 2H), 3.66
(t, 2H), 4.15 (t, 2H), 6.87 (d, 2H), 7.05 (s, 1H), 7.67 (t, 1H),
7.95 (d, 1H), 8.10 (t, 1H). Example 381 ##STR00439## 2-ethyl-N-{4-
[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+): 443.3;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.71 (m, 6H), 1.26 (m, 2H),
1.36 (m, 2H), 1.45 (m, 2H), 1.63 (m, 2H), 1.85 (m, 1H), 2.94 (s,
3H), 3.07 (q, 2H), 3.97 butyramide (s, 3H), 3.50 (q, 2H), 3.65 (t,
2H), 4.14 (t, 2H), 6.87 (d, 1H), 7.05 (s, 1H), 7.73 (t, 1H), 7.93
(d, 1H), 8.10 (t, 1H). Example 382 ##STR00440## N-{4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-3,3- dimethyl- Mass (M + H.sup.+): 443.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.88 (s, 9H), 1.44 (m, 2H),
1.62 (m, 2H), 1.88 (s, 2H), 2.95, (s, 3H), 3.04 (m, 2H), 3.28 (s,
3H), 3.52 (q, 2H), 3.66, butyramide (t, 2H), 4.15 (t, 2H), 6.86
(dd, 1H), 7.06 (s, 1H), 7.64 (t, 1H), 7.94 (d, 1H), 8.09 (t, 1H).
Example 383 ##STR00441## 4-methyl- pentanoic acid{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- Mass (M + H.sup.+): 443.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.0.78 (d, 6H), 1.31 (m, 2H), 1.42 (m, 3H), 1.65 (m, 2H),
1.99 (m, 2H), 2.95 (s, 3H), 3.04 (q, 2H), 3.27 (s, 3H), 3.50
butyl}-amide (q, 2H), 3.65 (t, 2H), 4.15 (t, 2H), 6.87 (d, 1H),
7.06 (s, 1H), 7.71 (t, 1H), 7.96 (d, 1H), 8.09 (t, 1H). Example 384
##STR00442## acetic acid- 1-{4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butylcarbamo-
Mass (M + H.sup.+): 473.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.1.39 (s, 6H), 1.44 (m, 2H), 1.60 (m, 2H), 1.94 (s, 3H), 2.94
(s, 3H), 3.05 (q, 2H), 3.29 (s, 3H), 3.48 (q, 2H), 3.65
yl}-1-methyl- (t, 2H), 4.14 (t, ethylester 2H), 6.85 (dd, 1H), 7.05
(s, 1H), 7.66 (t, 1H), 7.94 (d, 1H), 8.06 (t, 1H). Example 385
##STR00443## 2-hydroxy-N- {4-(7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino)- butyl}-2- Mass (M
+ H.sup.+): 431.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.18 (s,
6H), 1.47 (m, 2H), 1.61 (m, 2H), 2.94 (s, 3H), 3.07 (q, 2H), 3.29
(s, 3H), 3.50 (q, 2H), 3.65 (t, 2H), 4.15 methyl- (t, 2H), 5.24 (s,
propionamide 1H), 6.85 (dd, 1H), 7.05 (s, 1H), 7.60 (t, 1H), 7.94
(dd, 1H), 8.09 (t, 1H). Example 386 ##STR00444## acetic acid-
{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butylcarbamo- Mass (M + H.sup.+): 445.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.1.45 (m, 2H), 1.62 (m, 2H),
2.03 (s, 3H), 2.95 (s, 3H), 3.10 (m, 2H), 3.29
(s, 3H), 3.51 (m, 2H), 3.65 (m, 2H), 4.15 yl}-methylester (m, 2H),
4.37 (s, 2H), 6.87 (d, 1H), 7.07 (s, 1H), 7.94 (s, 1H), 7.96 (d,
1H), 8.10 (t, 1H). Example 387 ##STR00445## 2-hydroxy-N- {4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- Mass (M + H.sup.+): 403.2; .sup.1H NMR (500
MHz, DMSO- d6): .delta.1.49 (m, 2H), 1.62 (m, 2H), 2.94 (s, 3H),
3.12 (m, 2H), 3.29 (s, 3H), 3.51 (m, 2H), 3.65 (m, 2H), 3.73 (m,
2H), 4.15 acetamide (d, 2H), 5.39 (t, 1H), 6.85 (d, 1H), 7.06 (s,
1H), 7.69 (t, 1H), 7.93 (d, 1H), 8.08 (t, 1H). Example 388
##STR00446## 2-(R)- hydroxy-N- {4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 445.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.68 (d,
3H), 0.83 (d, 3H), 1.47 (m, 2H), 1.62 (m, 2H), 1.91 (m, 1H), 2.95
(s, 3H), 3.10 (m, 2H), 3.29 (s, 3H), 3.51 butyl}-3- (m, 2H), 3.61
(m, methyl- 1H), 3.66 (m, 2H), butyramide 4.15 (m, 2H), 5.24 (d,
1H), 6.86 (d, 1H), 7.06 (s, 1H), 7.66 (t, 1H), 7.94 (s, 1H), 8.09
(t, 1H). Example 389 ##STR00447## 2-(S)- hydroxy-N- {4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- Mass (M + H.sup.+): 445.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.0.69 (d, 3H), 0.83 (d, 3H), 1.48 (m, 2H), 1.61 (m, 2H),
1.91 (m, 1H), 2.94 (s, 3H), 3.13 (q, 2H), 3.50 (q, 2H), 3.60
butyl}-3- (d, 1H), 3.66 (t, methyl- 2H), 4.15 (t, 2H), butyramide
5.23 (d, 1H), 6.86 (d, 1H), 7.06 (s, 1H), 7.65 (t, 1H), 7.93 (d,
1H), 8.10 (t, 1H). Example 390 ##STR00448## 2-(R)- methoxy-N-
{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- Mass (M + H.sup.+): 449.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.79 (m, 6H), 1.48 (m, 2H), 1.62 (m,
2H), 1.80 (m, 1H), 2.95 (s, 3H), 3.15 (q, 2H), 3.17 (s, 3H), 3.29
(d, 2H), 3.50 butyl}-3- (q, 2H), 3.66 (t, methyl- 2H), 4.15 (t,
2H), butyramide 6.87 (d, 1H), 7.05 (s, 1H), 7.79 (t, 1H), 7.95 (d,
1H), 8.10 (t, 1H). Example 391 ##STR00449## 2,2- difluoro-N-
{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- Mass (M + H.sup.+): 451.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.83 (t, 3H), 1.52 (m, 2H), 1.60 (m,
2H), 1.97 (m, 2H), 2.94 (s, 3H), 3.15 (q, 2H), 3.28 (s, 3H), 3.52
(q, 2H), 3.65 butyl}- (t, 2H), 4.14 (t, butyramide 2H), 6.86 (dd,
1H), 7.05 (s, 1H), 7.94 (d, 1H), 8.10 (t, 1H), 8.64 (t, 1H).
Example 392 ##STR00450## 3,3,3- trifluoro-N- {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- Mass (M + H.sup.+): 483.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.27 (s, 6H), 1.49 (m, 2H), 1.61 (m, 2H), 2.95 (s, 3H),
3.11 (q, 2H), 3.29 (s, 3H), 3.49 (q, 2H), 3.66 (t, 2H), 4.14
butyl}-2,2- (t, 2H), 6.87 (d, dimethyl- 1H), 7.06 (s, 1H),
propionamide 7.86 (t, 1H), 7.96 (d, 1H), 8.10 (t, 1H). Example 393
##STR00451## 3-cyclopentyl- N-{4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 469.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.97 (m,
2H), 1.32 (m, 2H), 1.44 (m, 4H), 1.51 (m, 2H), 1.62 (m, 5H), 2.00
(m, 2H), 2.95 (s, 3H), butyl}- 3.04 (m, 2H), 3.29 propionamide (s,
3H), 3.52 (q, 2H), 3.66 (t, 2H), 4.15 (t, 2H), 6.86 (dd, 1H), 7.06
(s, 1H), 7.69 (t, 1H), 7.94 (d, 1H), 8.09 (t, 1H). Example 394
##STR00452## N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+):
459.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.10 (t, 3H), 1.13
(q, 2H), 1.47 (m, 2H), 1.64 (m, 2H), 2.95 (s, 3H), 3.06 (m, 2H),
3.14 (s, 2H), malonamic 3.29 (s, 3H), 3.52 acid ethylester (q, 2H),
3.66 (t, 2H), 4.15 (t, 2H), 6.86 (dd, 1H), 7.06 (s, 1H), 7.95 (d,
1H), 8.03 (t, 1H), 8.10 (t, 1H). Example 395 ##STR00453##
N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- malonamic acid Mass (M +
H.sup.+): 429.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.64 (m,
2H), 1.71 (m, 2H), 2.76 (m, 2H), 2.95 (s, 3H), 3.14 (m, 2H), 3.30
(s, 3H), 3.55 (m, 2H), 3.66 (t, 2H), 4.17 (t, 2H), 6.86 (dd, 1H),
7.07 (s, 1H), 7.80 (t, 1H), 7.88 (br, 1H), 7.95 (d, 1H), 8.95 (t,
1H). Example 396 ##STR00454## (1-{4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]-
butylcarbamo- Mass (M + H.sup.+): 544.2; .sup.1H NMR (500 MHz,
DMSO- d6): .delta.0.75 (m, 6H), 1.32 (s, 9H), 1.45 (q, 2H), 1.63
(q, 2H), 1.82 (m, 1H), 2.95 (s, 3H), 3.12 (m, 2H), yl}-2-methyl-
3.28 (s, 3H), 3.52 propyl)- (q, 2H), 3.65 (t, carbamic 2H), 3.66
(m, 1H), acid-tert- 4.15 (t, 2H), 6.50 butylester (d, 1H), 6.86
(dd, 1H), 7.06 (s, 1H), 7.79 (t, 1H), 7.94 (d, 1H), 8.09 (t, 1H).
Example 397 ##STR00455## 2-amino-N- {4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3-
Mass (M + H.sup.+): 444.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.0.71 (d, 3H), 0.79 (d, 3H), 1.46 (q, 2H), 1.63 (q, 2H), 1.80
(m, 1H), 1.98 (br, 2H), 2.85 (m, 1H), 2.95 (s, 3H), 3.09 methyl-
(m, 2H), 3.29 (s, butyramide 3H), 3.52 (q, 2H), 3.65 (t, 2H), 4.15
(t, 2H), 6.86 (dd, 1H), 7.05 (s, 1H), 7.79 (t, 1H), 7.94 (d, 1H),
8.09 (t, 1H). Example 398 ##STR00456## (S)-(1-{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butylcarbamo- Mass (M + H.sup.+): 544.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.77 (m, 6H), 0.82 (m, 6H), 1.44 (q,
2H), 1.63 (q, 2H), 1.78 (m, 1H), 1.86 (m, 1H), 2.95 (s, 3H),
yl}-2-methyl- 3.05 (m, 2H), 3.29 propyl)- (s, 3H), 3.49 (q,
carbamic acid 2H), 3.65 (t, 2H), isobutylester 3.66 (m, 1H), 4.15
(t, 2H), 6.85 (dd, 1H), 6.97 (d, 1H), 7.05 (s, 1H), 7.85 (t, 1H),
7.94 (d, 1H), 8.09 (t, 1H). Example 399 ##STR00457## (S)-(1-{4-[7-
(2-methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butylcarbamo- Mass (M + H.sup.+): 530.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.76 (m, 3H), 1.47 (m, 4H),
1.65 (q, 2H), 1.85 (m, 1H), 2.95 (s, 3H), 3.04 (m, 2H), 3.29 (s,
3H), yl}-2-methyl- 3.50 (q, 2H), 3.65 propyl)- (t, 2H), 3.66 (m,
carbamic acid 1H), 3.83 (q, 2H), propylester 4.15 (t, 2H), 6.85
(dd, 1H), 6.89 (d, 1H), 7.05 (s, 1H), 7.84 (t, 1H), 7.94 (d, 1H),
8.08 (t, 1H). Example 400 ##STR00458## (S)-(1-{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butylcarbamo- yl}-2-methyl- Mass (M + H.sup.+): 530.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.76 (m, 6H), 1.10 (m, 6H),
1.45 (q, 2H), 1.63 (q, 2H), 1.84 (m, 1H), 2.95 (s, 3H), 3.04 (m,
2H), 3.29 (s, 3H), 3.49 propyl)- (q, 2H), 3.65 (t, carbamic acid
2H), 3.66 (m, 1H), isopropylester 4.15 (t, 2H), 4.67 (m, 1H), 6.78
(d, 1H), 6.85 (dd, 1H), 7.06 (s, 1H), 7.83 (t, 1H), 7.94 (d, 1H),
8.10 (t, 1H). Example 401 ##STR00459## (S)-N-{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-3- methyl-2-(3- methyl-butyryl- amino)- Mass (M
+ H.sup.+): 528.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.77 (d,
6H), 0.81 (d, 6H), 1.45 (q, 2H), 1.63 (q, 2H), 1.82 (m, 1H), 1.88
(m, 1H), 1.98 (m, 2H), 2.95 (s, 3H), 3.05 (m, 2H), 3.29 (s, 3H),
3.49 (q, 2H), butyramide 3.65 (t, 2H), 4.04 (m, 1H), 4.15 (t, 2H),
6.85 (dd, 1H), 7.05 (s, 1H), 7.69 (d, 1H), 7.88 (t, 1H), 7.93 (d,
1H), 8.08 (t, 1H). Example 402 ##STR00460## (S)-2-(2,2- dimethyl-
propionyl- amino)-N-{4- [7-(2-methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 528.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.75 (m,
6H), 1.05 (s, 9H), 1.46 (q, 2H), 1.63 (q, 2H), 1.90 (m, 1H), 2.95
(s, 3H), 3.04 (m, 2H), 3.29 (s, 3H), 3.51 (q, 2H), 3.66 (t,
butyl}-3- 2H), 4.02 (m, 1H), methyl- 4.15 (t, 2H), 6.87 butyramide
(dd, 1H), 6.97 (d, 1H) 7.10 (s, 1H), 7.88 (t, 1H), 7.95 (d, 1H),
8.18 (t, 1H). Example 403 ##STR00461## 2-(S,R)- hydroxy-N-
(1-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- Mass (M + H.sup.+): 544.2; .sup.1H NMR (500 MHz,
DMSO- d6): .delta.0.77 (t, 6H), 0.79 (d, 3H), 0.88 (d, 3H), 1.50
(q, 2H), 1.66 (q, 2H), 1.89 (m, 1H), 1.97 (m, 1H), 4-ylamino]- 2.96
(s, 3H), 3.11 butylcarbamo- (m, 2H), 3.31 (s, yl}-2-methyl- 3H),
3.54 (q, 2H), propyl)-3- 3.67 (m, 3H), 4.13 methyl- (m, 1H), 4.17
(t, butyramide 2H), 5.35 (d, 1H), 6.87 (d, 1H), 7.08 (s, 1H), 7.37
(d, 1H), 7.86 (t, 1H), 7.88 (t, 1H), 7.96 (d, 1H). Example 404
##STR00462## 2-(S,S)- hydroxy-N- (1-{4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- Mass (M + H.sup.+):
544.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.65 (d, 3H), 0.77
(t, 6H), 0.84 (d, 3H), 1.45 (q, 2H), 1.63 (q, 2H), 1.84 (m, 1H),
1.86 (m, 1H), 4-ylamino]- 2.95 (s, 3H), 3.05 butylcarbamo- (m, 2H),
3.29 (s, yl}-2-methyl- 3H), 3.49 (q, 2H), propyl)-3- 3.66 (t, 2H),
3.68 methyl- (m, 1H), 4.08 (m, butyramide 1H), 4.15 (t, 2H), 5.35
(d, 1H), 6.86 (dd, 1H), 7.06 (d, 1H), 7.41 (d, 1H), 7.74 (d, 1H),
7.99
(t, 1H), 8.09 (t, 1H). Example 405 ##STR00463## 2-(S)- methanesul-
fonylamino- {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- Mass (M + H.sup.+): 522.2; .sup.1H NMR
(500 MHz, DMSO- d6): .delta.0.79 (m, 6H), 1.48 (q, 2H), 1.65 (q,
2H), 1.82 (m, 1H), 2.74 (s, 3H), 2.95 (s, 3H), 3.11 (m, 2H), 3.29
(s, 3H), 3.47 4-ylamino]- (m, 1H), 3.52 (q, butyl}-3- 2H), 3.66 (t,
2H), methyl- 4.15 (t, 2H), 6.86 butyramide (dd, 1H), 7.05 (s, 1H),
7.12 (d, 1H), 7.94 (d, 1H), 8.05 (t, 1H), 8.13 (t, 1H). Example 406
##STR00464## N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-2- thiophene-2-
yl-acetamide Mass (M + H.sup.+): 469.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.46 (m, 2H), 1.63 (m, 2H), 2.95 (s, 3H), 3.07 (q, 2H),
3.29 (s, 3H), 3.49 (q, 2H), 3.56 (s, 2H), 3.65 (t, 2H), 4.15 (t,
2H), 6.83 (s, 1H), 6.87 (m, 2H), 7.06 (s, 1H), 7.29 (d, 1H), 7.95
(d, 1H), 8.02 (t, 2H), 8.09 (t, 2H). Example 407 ##STR00465##
2-furan-2- yl-N-{4-[7- (2-methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+):
453.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.47 (m, 2H), 1.63
(m, 2H), 2.95 (s, 3H), 3.08 (q, 2H), 3.27 (s. 3H), 3.41 (s, 2H),
3.50 (q, 2H), 3.66 (t, 2H), 4.15 acetamide (t, 2H), 6.11 (s, 1H),
6.29 (s, 1H), 6.87 (d, 1H), 7.07 (s, 1H), 7.45 (s, 1H), 7.96 (d,
2H), 8.10 (t, 1H). Example 408 ##STR00466## N-{4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- benzamide Mass (M + H.sup.+): 449.2; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.1.60 (m, 2H), 1.69 (m, 2H), 2.94
(s, 3H), 3.28 (s, 3H), 3.29 (m, 2H), 3.55 (q, 2H), 3.65 (t, 2H),
4.13 (t, 2H), 6.48 (d, 1H), 7.04 (s, 1H), 7.39 (t, 2H), 7.46 (t,
1H), 7.77 (dd, 2H), 7.94 (d, 1H), 8.12 (t, 1H), 8.41 (t, 1H).
Example 409 ##STR00467## 2-fluoro-N- {4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
Mass (M + H.sup.+): 467.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.1.59 (m, 2H), 1.70 (m, 2H), 2.96 (s, 3H), 3.28 (m, 2H), 3.29
(s, 3H), 3.57 (q, 2H), 3.65 (t, 2H), 4.14 (t, 2H), 6.89 benzamide
(dd, 1H), 7.15 (t, 1H), 7.20 (t, 1H), 7.22 (m, 2H), 7.45 (t, 1H),
7.53 (t, 1H), 7.96 (d, 1H), 8.28 (t, 1H). Example 410 ##STR00468##
3-fluoro-N- {4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+):
467.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.58 (m, 2H), 1.69
(m, 2H), 2.94 (s, 3H), 3.26 (m, 2H), 3.28 (s, 3H), 3.52 (q, 1 2H),
3.64 (t, 2H), 4.13 (t, 2H), 6.87 benzamide (d, 1H), 7.04 (s, 1H),
7.22 (dd, 2H), 7.85 (dd, 2H), 7.94 (d, 1H), 8.12 (t, 1H), 8.43 (t,
1H). Example 411 ##STR00469## 2-chloro-N- {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- Mass (M + H.sup.+): 483.2; .sup.1H NMR (500
MHz, DMSO- d6): .delta.1.58 (m, 2H), 1 .72 (m, 2H), 2.95 (s, 3H),
3.24 (m, 2H), 3.29 (s, 3H), 3.53 (q, 2H), 3.65 (t, 2H), 4.14 (t,
2H), 6.86 benzamide (dd, 1H), 7.07 (d, 1H), 7.29 (t, 1H), 7.34 (dd,
1H), 7.38 (dd, 1H), 7.41 (d, 1H), 7.95 (d, 1H), 8.12 (t, 1H), 7.36
(t, 1H). Example 412 ##STR00470## 2-chloro-N- {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- Mass (M + H.sup.+): 483.2; .sup.1H NMR (500
MHz, DMSO- d6): .delta.1.58 (m, 2H), 1.69 (m, 2H), 2.94 (s, 3H),
3.20 (q, 2H), 3.29 (s, 3H), 3.50 (q, 2H), 3.66 (t, 2H), 4.13 (t,
2H), 6.87 benzamide (d, 1H), 7.04 (d, 1H), 7.47 (d, 2H), 7.80 (d,
2H), 7.95 (d, 1H), 8.10 (t, 1H), 8.49 (t, 1H). Example 413
##STR00471## 2,3- dichloro-N- {4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 518.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.58 (m,
2H), 1.72 (m, 2H), 2.95 (s, 3H), 3.25 (q, 2H), 3.28 (s, 3H), 3.50
(q, 2H), 3.66 (t, 2H), 4.14 (t, 2H), 6.87 butyl}- (d, 1H), 7.07 (s,
benzamide 1H), 7.31 (m, 2H), 7.62 (d, 1H), 7.96 (d, 1H), 8.13 (t,
1H), 8.47 (t, 1H). Example 414 ##STR00472## 2-methoxy-N- {4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- benzamide Mass (M + H.sup.+): 479.2; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.1.57 (m, 2H), 1.70 (m, 2H), 2.94
(s, 3H), 3.28 (s, 3H), 3.31 (m, 2H), 3.54 (q, 2H), 3.64 (t, 2H),
3.78 (s, 3H), 4.12 (t, 2H), 6.85 (dd, 1H), 6.95 (t, 1H), 7.05 (t,
2H), 7.39 (t, 1H), 7.65 (d, 1H), 7.94 (d, 1H), 8.12 (m, 2H).
Example 415 ##STR00473## N-{4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-4-nitro-
butyramide Mass (M + H.sup.+): 494.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.61 (m, 2H), 1.71 (m, 2H), 2.94 (s, 3H), 3.27 (s, 3H),
3.28 (q, 2H), 3.55 (q, 2H), 3.65 (t, 2H), 4.12 (t, 2H), 6.86 (d,
1H), 7.03 (s, 1H), 7.93 (d, 2H), 7.62 (d, 1H), 7.96 (d, 1H), 8.00
(d, 2H), 8.10 (t, 1H), 8.24 (d, 2H), 8.74 (t, 1H). Example 416
##STR00474## pyridine-2- carboxylic acid-{4-[7- (2-methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- Mass (M + H.sup.+): 450.2; .sup.1H NMR (500 MHz, DMSO-
d6): .delta.1.61 (m, 2H), 1.69 (m, 2H), 2.95 (s, 3H), 3.29 (s, 3H),
3.33 (m, 2H), 3.53 (m, 2H), 3.66 (t, 2H), 4.15 (t, 2H), 6.88
butyl}-amide (dd, 1H), 7.05 (s, 1H), 7.54 (m, 1H), 7.93 (m, 1H),
7.97 (m, 2H), 8.11 (t, 1H), 8.56 (d, 1H), 8.75 (t, 1H). Example 417
##STR00475## N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- nicotinamide Mass (M
+ H.sup.+): 450.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.63 (m,
2H), 1.73 (m, 2H), 2.95 (s, 3H), 3.31 (s, 3H), 3.33 (m, 2H), 3.53
(m, 2H), 3.66 (t, 2H), 4.15 (t, 2H), 6.88 (dd, 1H), 7.07 (s, 1H),
7.42 (m, 1H), 7.94 (m, 1H), 7.96 (d, 1H), 8.10 (d, 1H), 8.49 (t,
1H), 8.64 (t, 1H), 8.95 (s, 1H). Example 418 ##STR00476##
N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-iso- nicotinamide Mass (M +
H.sup.+): 450.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.60 (m,
2H), 1.70 (m, 2H), 2.95 (s, 3H), 3.28 (s, 3H), 3.31 (m, 2H), 3.53
(m, 2H), 3.65 (t, 2H), 4.13 (t, 2H), 6.86 (dd, 1H), 7.05 (s, 1H),
7.68 (m, 2H), 7.95 (d, 1H), 8.12 (t, 1H), 8.65 (m, 2H), 8.71 (t,
1H). Example 419 ##STR00477## 6-chloro-N- {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- Mass (M + H.sup.+): 483.95; .sup.1H NMR (500
MHz, DMSO- d6): .delta.1.61 (m, 2H), 1.70 (m, 2H), 2.94 (s, 3H),
3.28 (s, 3H), 3.30 (q, 2H), 3.52 (q, 2H), 3.66 (t, 2H), 4.14 (t,
2H), 6.86 (d, nicotinamide 1H), 7.04 (s, 1H), 7.57 (d, 1H), 7.95
(d, 1H), 8.11 (t, 1H), 8.15 (d, 1H), 8.76 (s, 1H). Example 420
##STR00478## N-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-2- phenyl- acetamide
Mass (M + H.sup.+): 463.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.1.46 (m, 2H), 1.62 (m, 2H), 2.95 (s, 3H), 3.05 (q, 2H), 3.25
(s, 3H), 3.28 (s, 2H), 3.50 (q, 2H), 3.64 (t, 2H), 4.13 (t, 2H),
6.86 (d, 2H), 7.06 (s, 1H), 7.15 (t, 1H), 7.20 (m, 1H), 7.22 (m,
3H), 7.95 (d, 1H), 7.98 (t, 1H), 8.09 (t, 1H). Example 421
##STR00479## 3-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri-
azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-1,1- dimethyl-urea
Mass (M + H.sup.+): 416.2; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.1.45 (m, 2H), 1.61 (m, 2H), 2.95 (s, 3H), 3.01 (q, 2H), 3.29
(s, 3H), 3.50 (q, 2H), 3.66 (t, 2H), 4.16 (t, 2H), 6.19 (t, 1H),
6.87 (d, 1H), 7.06 (s, 1H), 7.95 (d, 1H), 8.07 (t, 1H). Example 422
##STR00480## 1-isopropyl-3- {4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-urea Mass
(M + H.sup.+): 430.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.0.95
(d, 6H), 1.41 (m, 2H), 1.61 (m, 2H), 2.94 (s, 3H), 2.98 (q, 2H),
3.29 (s, 3H), 3.50 (q, 2H), 3.60 (m, 1H), 3.66 (q, 2H), 4.15 (t,
2H), 5.53 (d, 1H), 5.63 (t, 1H), 6.86 (d, 1H), 7.06 (s, 1H), 7.94
(d, 1H), 8.10 (t, 1H). Example 423 ##STR00481## 1-ethyl-3-{4-
[7-(2-methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-urea Mass (M + H.sup.+): 416.2;
.sup.1H NMR (500 MHz, DMSO- d6): .delta.0.92 (t, 3H), 1.41 (m, 2H),
1.60 (m, 2H), 2.94 (q, 2H), 2.94 (s, 3H), 2.95 (q, 2H), 3.29 (s,
3H), 3.52 (q, 2H), 3.65 (t, 2H), 4.15 (t, 2H), 5.66 (t, 1H), 5.74
(t, 1H), 6.87 (dd, 1H), 7.07 (s, 1H), 7.94 (d, 1H), 8.09 (t, 1H).
Example 424 ##STR00482## 1-tert-butyl-3- {4-[7-(2- methoxy-
ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-urea Mass (M + H.sup.+): 444.2; .sup.1H NMR (500
MHz, DMSO- d6): .delta.1.16 (s, 9H), 1.39 (m, 2H), 1.60 (m, 2H),
2.94 (q, 2H), 2.95 (s, 3H), 3.28 (s, 3H), 3.52 (q, 2H), 3.66 (t,
2H), 4.15 (t, 2H), 5.49 (t, 1H), 5.57 (t, 1H), 6.87 (dd, 1H), 7.07
(s, 1H), 7.95 (d, 1H), 8.10 (t, 1H). Example 425 ##STR00483##
morpholine-4- carboxylic acid-{4-[7-(2- methoxy- ethoxy)-1- methyl-
[1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- Mass (M +
H.sup.+): 458.3; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.47 (m,
2H), 1.62 (m, 2H), 2.94 (s, 3H), 3.05 (q, 2H), 3.17 (m, 4H), 3.29
(s, 3H), 3.45 (q, 2H), 3.47 (m, 4H), 3.65 butyl}-amide (q, 2H),
4.15 (q, 2H), 6.46 (t, 1H), 6.86 (d, 1H), 7.05 (s, 1H), 7.92 (d,
1H), 8.08 (t, 1H). Example 426 ##STR00484## 1-cyclohexyl-
3-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-urea
Mass (M + H.sup.+): 470.3; .sup.1H NMR (500 MHz, DMSO- d6):
.delta.0.99 (m, 2H), 1.09 (m, 1H), 1.18 (m, 2H), 1.40 (t, 2H), 1.46
(m, 1H), 1.58 (m, 2H), 1.61 (m, 2H), 1.69 (m, 2H), 2.95 (s, 3H),
2.97 (t, 2H), 3.28 (m, 1H), 3.29 (s, 1H), 3.49 (q, 2H), 3.65 (t,
2H), 4.15 (t, 2H), 5.57 (d, 1H), 5.63 (t, 1H), 6.86 (d, 1H), 7.06
(s, 1H), 7.95 (d, 1H), 8.09 (t, 1H). Example 427 ##STR00485##
3-{4-[7-(2- methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-1- phenyl-urea Mass (M +
H.sup.+): 464.2; .sup.1H NMR (500 MHz, DMSO- d6): .delta.1.49 (m,
2H), 1.66 (m, 2H), 2.95 (s, 3H), 3.10 (m, 2H), 3.28 (s, 3H), 3.53
(m, 2H), 3.64 (t, 2H), 4.14 (t, 2H), 6.09 (t, 1H), 6.83 (t, 1H),
6.85 (dd, 1H), 7.07 (s, 1H), 7.16 (m, 2H), 7.32 (m, 2H), 7.74 (d,
1H), 8.13 (t, 1H), 8.33 (t, 1H). Example 428 ##STR00486## {4-[7-(2-
methoxy- ethoxy)-1- methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- thiocarbamic Mass (M + H.sup.+): 447.2; .sup.1H
NMR (500 MHz, DMSO- d6): .delta.1.19 (d, 6H), 1.47 (m, 2H), 1.61
(m, 2H), 2.95 (s, 3H), 3.10 (m, 2H), 3.26 (s, 3H), 3.39 (m, 1H),
3.51 (m, 2H), 3.66 acid-S- (m, 2H), 4.15 (m, isopropylester 2H),
6.87 (d, 1H), 7.07 (s, 1H), 7.94 (s, 1H), 7.96 (d, 1H), 8.10 (t,
1H). Example 429 ##STR00487## N-{4-[7-(2- methoxy- ethoxy)-1-
methyl- [1,2,4]tri- azolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
methanesulfon- Mass (M + H.sup.+): 416.2; .sup.1H NMR (500 MHz,
DMSO- d6): .delta.1.53 (m, 2H), 1.67 (m, 2H), 2.83 (s, 3H), 2.96
(s, 3H), 3.01 (q, 2H), 3.29 (s, 3H), 3.51 (q 2H), 3.65 (t, 2H),
4.14 amide (t, 2H), 6.86 (d, 1H), 6.91 (t, 1H), 7.06 (s, 1H), 7.92
(d, 1H), 8.11 (t, 1H).
<Preparative Example 24> Preparation of
{4-[3-hydrazino-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino]-butyl-
}-carbamic acid-tert-butylester
##STR00488##
[1429]
{4-[3-hydrazino-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino]-
-butyl}-carbamic acid-tert-butylester, a target compound of
Preparative Example 24 was obtained by the same manner as described
in Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-(2-morpholine-4-yl-ethoxy)-quinoxaline
[1430] Mass (M+H.sup.+): 328.0
[1431] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.62 (brm, 2H), 2.90
(brm, 2H), 3.76 (brm, 4H), 4.27 (brm, 2H), 7.29 (s, 1H), 7.44 (d,
1H), 7.89 (d, 1H).
Step 2: Preparation of
{4-[3-chloro-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino]-butyl}-c-
arbamic acid-tert-butylester
[1432] Mass (M+H.sup.+): 500.1
[1433] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.40 (m,
2H), 1.57 (m, 2H), 2.46 (brm, 4H), 2.69 (t, 2H), 2.91 (m, 2H), 3.40
(q, 2H), 3.54 (t, 4H), 4.16 (t, 2H), 6.74 (t, 1H), 6.98 (dd, 1H),
7.01 (s, 1H), 7.34 (t, 1H), 7.56 (d, 1H)
Step 3: Preparation of
{4-[3-hydrazino-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino]-butyl-
}-carbamic acid-tert-butylester
[1434] Mass (M+H.sup.+): 476.3
[1435] Examples of the compounds synthesized using
{4-[3-hydrazino-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino]-butyl-
}-carbamic acid-tert-butyl ester prepared in Preparative Example 24
are shown in Table 26 below.
TABLE-US-00026 TABLE 26 Ex- ample Structure Name Data Ex- ample 430
##STR00489## {4-[1- methyl-7-(2- morpholine- 4-yl- ethoxy)-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic
Mass (M + H.sup.+): 500.3; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.32 (s, 9H), 1.43 (m, 2H), 1.61 (m, 2H), 2.68 (t, 2H), 2.92
(m, 2H), 2.94 acid-tert- (t, 4H), 3.27 butylester (s, 3H), 3.48 (m,
2H), 3.55 (t, 4H), 4.14 (t, 2H), 6.74 (t, 1H), 6.85 (dd, 1H), 7.08
(s, 1H), 7.93 (d, 1H), 8.08 (t, 1H). Ex- ample 431 ##STR00490##
N.sup.1-{4-[1- methyl-7-(2- morpholine- 4-yl- ethoxy)- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4-yl]- Mass (M + H.sup.+): 400.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.61 (m, 2H), 1.69 (m, 2H), 2.81 (m,
2H), 2.96 butane-1,4- (s, 3H), 3.26 diamine (brm, 2H), 3.53
trifluoroacetic (brm, 4H), 3.58 acid (m, 2H), 3.72 (brm, 2H), 3.95
(brm, 2H), 4.43 (t, 2H), 6.93 (dd, 1H), 7.17 (d, 1H), 7.76 (brm,
2H), 8.00 (d, 1H), 8.29 (t, 1H). Ex- ample 432 ##STR00491##
3-methyl-N- {4-[1- methyl-7-(2- morpholine- 4-yl- ethoxy)-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- Mass (M +
H.sup.+): 484.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.43 (m, 2H), 1.62 (m, 2H), 1.86 (m, 2H), 1.92 (m, 1H), 2.46
butyramide (m, 4H), 2.69 (t, 2H), 2.94 (s, 3H), 3.04 (q, 2H), 3.49
(m, 2H), 3.55 (m, 4H), 4.14 (t, 2H), 6.85 (dd, H), 7.07 (s, 1H),
7.69 (t, 1H), 7.94 (d, 1H), 8.10 (t, 1H). Ex- ample 433
##STR00492## 2,2- dimethyl-N- {4-[1- methyl-7-(2- morpholine- 4-yl-
ethoxy)- [1,2,4]tria- zolo[4,3- a]quinoxaline- Mass (M + H.sup.+):
484.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.45
(m, 2H), 1.60 (m, 2H), 2.46 (brm, 4H), 2.68 4-ylamino]- (t, 2H),
2.94 butyl}- (s, 3H), 3.04 propionamide (q, 2H), 3.49 (q, 2H), 3.55
(t, 4H), 4.14 (t, 2H), 6.85 (dd, 1H), 7.06 (s, 1H), 7.37 (t, 1H),
7.93 (d, 1H), 8.08 (t, 1H). Ex- ample 434 ##STR00493## 2-(R)-
hydroxy-N- {4-[7-(2- morpholine- 4-yl- ethoxy)-1- methyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- Mass (M + H.sup.+): 500.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H),
1.46 (m, 1H), 1.61 (m, 1H), 1.90 4-ylamino]- (m, 1H), 2.68
butyl}-3- (t, 2H), 2.94 methyl- (s, 3H), 3.06 butyramide (m, 1H),
3.13 (m, 1H), 3.49 (m, 2H), 3.55 (t, 4H), 3.61 (t, 1H), 4.14 (t,
2H), 5.23 (d, 1H), 6.84 (d, 1H), 7.07 (s, 1H), 7.65 (t, 1H), 7.93
(d, 1H), 8.10 (t, 1H). Ex- ample 435 ##STR00494## 2-(S)- hydroxy-N-
{4-[7-(2- morpholine- 4-yl- ethoxy)-1- methyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- Mass (M + H.sup.+): 500.3; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.46 (m,
1H), 1.61 (m, 1H), 1.90 4-ylamino]- (m, 1H), 2.68 butyl}-3- (t,
2H), 2.94 methyl- (s, 3H), 3.06 butyramide (m, 1H), 3.13 (m, 1H),
3.49 (m, 2H), 3.55 (t, 4H), 3.61 (t, 1H), 4.14 (t, 2H), 5.23 (d,
1H), 6.84 (d, 1H), 7.07 (s, 1H), 7.65 (t, 1H), 7.93 (d, 1H), 8.10
(t, 1H). Ex- ample 436 ##STR00495## {4-[1- methyl-7-(2- morpholine-
4-yl- ethoxy)- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}- carbamic acid Mass (M + H.sup.+): 486.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.10 (d, 6H), 1.43 (m, 2H), 1.61 (m, 2H),
2.46 (m, 4H), 2.68 (t, 2H), 2.94 isopropylester (s, 3H), 2.96 (m,
2H), 3.49 (q, 2H), 3.55 (t, 4H), 4.14 (t, 2H), 4.68 (m, 1H), 6.85
(dd, 1H), 6.95 (t, 1H), 7.08 (s, 1H), 7.94 (d, 1H), 8.08 (t, 1H).
Ex- ample 437 ##STR00496## {4-[1- methyl-7-(2- morpholine- 4-yl-
ethoxy)- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-
carbamic Mass (M + H.sup.+): 512.3; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.40~1.64 (m, 10H), 1.71 (m, 2H), 2.46 (m, 4H), 2.68 (t,
2H), 2.94 (s, 3H), 2.99 (m, acid 2H), 3.49 (q, cyclopentylester
2H), 3.55 (t, 4H), 4.14 (t, 2H), 4.88 (m, 1H), 6.86 (dd, 1H), 6.94
(t, 1H), 7.08 (s, 1H), 7.94 (d, 1H), 8.07 (t, 1H). Ex- ample 438
##STR00497## N-{4-[1- methyl-7-(2- morpholine- 4-yl- ethoxy)-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-2-
thiophene-2- Mass (M + H.sup.+): 524.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.47 (m, 2H), 1.63 (m, 2H), 2.46 (m, 4H), 2.69 (m,
2H), 2.95 (s, 3H), 3.08 yl-acetamide (q, 2H), 3.52 (q, 2H), 3.55
(m, 4H), 3.56 (s, 2H), 4.14 (t, 2H), 6.83 (t, 1H), 6.86 (m, 2H),
7.08 (s, 1H), 7.29 (d, 1H), 7.94 (d, 1H), 8.02 (t, 1H), 8.09 (t,
1H). Ex- ample 439 ##STR00498## 2-chloro-N- {4-[1- methyl-7-(2-
morpholine- 4-yl- ethoxy)- [1,2,4]tria- zolo[4,3- a]quinoxaline-
4-ylamino]- butyl}- Mass (M + H.sup.+): 538.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.57 (m, 2H), 1.72 (m, 2H), 2.46 (m, 4H),
2.68 (t, 2H), 2.95 (s, 3H), 3.24 benzamide (t, 2H), 3.52 (m, 2H),
3.54 (t, 4H), 4.13 (t, 2H), 6.85 (dd, 1H), 7.09 (d, 1H), 7.29 (td,
1H), 7.33 (td, 1H), 7.37 (t, 1H), 7.41 (d, 1H), 7.94 (d, 1H), 8.12
(t, 1H), 8.36 (t, 1H).
<Preparative Example 25> Preparation of
[4-(3-hydrazino-7-ethoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00499##
[1437]
[4-(3-hydrazino-7-ethoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester, a target compound of Preparative Example 25,
was obtained by the same manner as described in Preparative Example
20.
Step 1: Preparation of 2,3-dichloro-6-ethoxy-quinoxaline
[1438] Mass (M+H.sup.+): 243.0
[1439] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (t, 3H), 4.18
(q, 2H), 7.41 (d, 1H), 7.51 (d, 1H), 7.92 (d, 1H).
Step 2: Preparation of
[4-(3-chloro-7-ethoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1440] Mass (M+H.sup.+): 395.1
[1441] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.42 (m, 9H), 1.60
(m, 2H), 1.70 (m, 2H), 3.20 (s, 2H), 3.56 (q, 2H), 4.11 (m, 2H),
6.97 (m, 1H), 6.99 (m, 1H), 7.62 (d, 1H).
Step 3: Preparation of
[4-(7-ethoxy-3-hydrazino-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1442] Mass (M+H.sup.+): 391.2
<Example 440> Preparation of
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester
##STR00500##
[1444] 0.64 g a target compound was obtained (47% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(7-ethoxy-3-hydrazino-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (1.28 g, 3.27 mmol) prepared in step 3 of
Preparative Example 25 was used.
[1445] Mass (M+H.sup.+): 415.0
[1446] .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.1.43 (m, 9H), 1.64
(m, 2H), 1.78 (m, 2H), 3.04 (s, 3H), 3.18 (m, 2H), 3.71 (m, 2H),
4.12 (m, 2H), 4.76 (s, 1H), 6.42 (s, 1H), 6.86 (d, 1H), 7.23 (s,
1H), 7.81 (d, 1H).
<Example 441> Preparation of
N.sup.1-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine dihydrochloride
##STR00501##
[1448] 510 mg of a target compound was obtained (86% yield) by the
same manner as described in Example 2, except that
[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-
-carbamic acid-tert-butylester (640 mg, 1.54 mmol) prepared in
Example 440 was used.
[1449] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.33 (t, 3H), 1.67 (m,
2H), 1.74 (m, 2H), 2.79 (m, 2H), 2.98 (s, 3H), 4.05 (m, 2H), 4.09
(m, 2H), 6.97 (t, 1H), 7.99 (m, 3H).
<Example 442> Preparation of
N-[4-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-buty-
l]-3-methyl-butyramide
##STR00502##
[1451] 17 mg of a target compound was obtained (13% yield) by the
same manner as described in Example 37, except that
N.sup.1-(7-ethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-butane-
-1,4-diamine dihydrochloride (130 mg, 0.33 mmol) prepared in
Example 441 was used.
[1452] Mass (M+H.sup.+): 399.2
[1453] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.78 (d, 6H), 1.31
(m, 3H), 1.45 (m, 2H), 1.60 (m, 2H), 1.87 (m, 4H), 2.94 (s, 3H),
3.04 (m, 2H), 3.49 (m, 2H), 4.07 (m, 2H), 6.82 (d, 1H), 2.02 (s,
1H), 7.73 (m, 1H), 7.94 (d, 1H), 8.07 (m, 1H).
[1454] The compounds shown in Table 27 below were prepared by the
same manner as described in Example 442.
TABLE-US-00027 TABLE 27 Example Structure Name Data Example 443
##STR00503## [4-(7- ethoxy-1- methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isopropylester
Mass (M + H.sup.+): 401.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.09 (t, 6H), 1.31 (m, 3H), 1.59 (m, 2H), 1.60 (m, 2H), 2.94
(s, 3H), 2.98 (m, 2H), 3.49 (m, 2H), 4.05 (m, 2H), 4.67 (m, 1H),
6.81 (d, 1H), 6.94 (s, 1H), 7.03 (s, 1H), 7.91 (d, 1H), 8.06 (m,
1H). Example 444 ##STR00504## [4-(7- ethoxy-1- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid isobutylester Mass (M + H.sup.+): 415.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.80 (d, 6H), 1.31 (t, 3H), 1.45 (m, 2H), 1.62 (m,
2H), 1.76 (m, 1H), 2.94 (s, 3H), 2.98 (m, 2H), 3.50 (m, 2H), 3.66
(m, 2H), 4.06 (m, 2H), 6.83 (d, 1H), 7.02 (s, 2H), 7.91 (s, 1H),
8.07 (m, 1H). Example 445 ##STR00505## [4-(7- ethoxy-1- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid cyclopentylester Mass (M + H.sup.+): 427.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.31 (m, 3H), 1.31 (t, 3H), 1.44 (m, 8H),
1.60 (m, 2H), 1.70 (m, 2H), 2.94 (s, 3H), 2.97 (m, 2H), 3.49 (m,
2H), 4.06 (m, 2H), 4.87 (m, 1H), 6.82 (d, 1H), 6.90 (s, 1H), 7.02
(s, 1H), 7.91 (d, 1H), 8.06 (m, 1H). Example 446 ##STR00506##
N-[4-(7- ethoxy-1- methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-2- thiophene- 2-yl- acetamide Mass (M +
H.sup.+): 439.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (t,
3H), 1.46 (m, 2H), 1.64 (m, 2H), 2.94 (s, 3H), 3.06 (m, 2H), 3.49
(m, 2H), 3.56 (m, 2H), 4.04 (q, 2H), 6.83 (m, 2H), 6.84 (m, 2H),
7.02 (s, 1H), 7.25 (s, 1H), 7.92 (d, 1H), 8.04 (m, 1H), 8.09 (m,
1H).
<Preparative Example 26> Preparation of
[4-(3-hydrazino-7-isopropoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00507##
[1456]
[4-(3-hydrazino-7-isopropoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester, a target compound of Preparative Example 26,
was obtained by the same manner as described in Preparative Example
20.
Step 1: Preparation of 2,3-dichloro-6-isopropoxy-quinoxaline
[1457] Mass (M+H.sup.+): 257.0
[1458] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.33 (d, 6H), 4.86
(m, 1H), 7.44 (s, 1H), 7.49 (dd, 1H), 7.93 (d, 1H).
Step 2: Preparation of
[4-(3-chloro-7-isopropoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1459] Mass (M+H.sup.+): 409.2
[1460] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.28 (d, 6H), 1.32
(s, 9H), 1.40 (m, 2H), 1.58 (m, 2H), 2.92 (m, 2H), 3.42 (m, 2H),
4.74 (m, 1H), 6.82 (t, 1H), 6.92 (d, 1H), 6.96 (s, 1H), 7.31 (t,
1H), 7.56 (d, 1H).
Step 3: Preparation of
[4-(3-hydrazino-7-isopropoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1461] Mass (M+H.sup.+): 405.1
<Example 447> Preparation of
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester
##STR00508##
[1463] 1.5 g of a target compound was obtained (27% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(3-hydrazino-7-isopropoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (5.14 g, 13 mmol) prepared in step 3 of
Preparative Example 24 was used.
[1464] Mass (M+H.sup.+): 429.0
[1465] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.25 (s, 9H), 1.32
(d, 6H), 1.42 (m, 2H), 1.61 (m, 2H), 2.91 (q, 2H), 2.94 (s, 3H),
3.50 (q, 2H), 4.69 (m, 1H), 6.80 (t, 1H), 6.82 (d, 1H), 7.03 (s,
1H), 7.93 (d, 1H), 8.05 (t, 1H)
<Example 448> Preparation of
N.sup.1-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid
##STR00509##
[1467] 1.3 g of a target compound was obtained (82% yield) by the
same manner as described in Example 58, except that
[4-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-bu-
tyl]-carbamic acid-tert-butylester (1.3 g, 3.0 mmol) prepared in
Example 447 was used.
[1468] Mass (M+H.sup.+): 329.2
[1469] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.27 (d, 6H), 1.59
(m, 2H), 1.69 (m, 2H), 2.83 (q, 2H), 2.05 (s, 3H), 3.53 (q, 2H),
4.69 (m, 2H), 6.84 (d, 1H), 7.03 (s, 1H), 7.61 (brs, 2H), 7.36 (d,
1H), 8.19 (brs, 1H).
<Example 449> Preparation of
N-[-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-3-methyl-butyramide
##STR00510##
[1471] 67 mg of a target compound was obtained (57% yield) by the
same manner as described in Example 37, except that
N.sup.1-(7-isopropoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-bu-
tane-1,4-diamine ditrifluoroacetic acid (150 mg, 0.3 mmol) prepared
in Example 448 was used.
[1472] Mass (M+H.sup.+): 413.2
[1473] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.27 (d,
6H), 1.45 (m, 2H), 1.62 (m, 2H), 1.87 (d, 2H), 1.89 (m, 1H), 2.94
(s, 3H), 3.05 (q, 2H), 3.50 (q, 2H), 4.70 (m, 1H), 6.83 (d, 1H),
7.03 (s, 1H), 7.69 (t, 1H), 7.94 (d, 1H), 8.06 (t, 1H).
[1474] The compounds shown in Table 28 below were prepared by the
same manner as described in Example 449.
TABLE-US-00028 TABLE 28 Example Structure Name Data Example 450
##STR00511## N-[4-(7- isopropoxy- 1-methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-2- methyl- butyramide Mass (M +
H.sup.+): 413.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.73 (t,
3H), 0.91 (d, 3H), 1.27 (m, 2H), 1.30 (d, 6H), 1.44 (m, 2H), 1.62
(m, 2H), 2.06 (m, 1H), 2.94 (s, 3H), 3.03 (q, 2H), 3.50 (q, 2H),
4.69 (m, 2H), 6.83 (d, 1H), 7.03 (s, 1H), 7.67 (t, 1H), 7.94 (d,
1H), 8.06 (t, 1H). Example 451 ##STR00512## N-[4-(7- isopropoxy-
1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-2-
thiophene- 2-yl- acetamide Mass (M + H.sup.+): 453.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.26 (d, 6H), 1.47 (m, 2H), 1.63 (m,
2H), 2.94 (s, 3H), 3.06 (q, 2H), 3.31 (q, 2H), 3.56 (s, 2H), 4.69
(m, 1H), 6.83 (m, 1H), 6.87 (m, 2H), 7.04 (s, 1H), 7.26 (d, 1H),
7.94 (d, 1H), 8.02 (t, 1H), 8.06 (t, 1H). Example 452 ##STR00513##
[4-(7- isopropoxy- 1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid isopropylester Mass (M +
H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.09 (d,
6H), 1.27 (d, 6H), 1.43 (m, 2H), 1.65 (m, 2H), 2.94 (s, 3H), 3.05
(q, 2H), 3.50 (q, 2H), 4.70 (m, 2H), 6.83 (d, 1H), 6.95 (t, 1H),
7.04 (s, 1H), 7.94 (d, 1H), 8.05 (t, 1H). Example 453 ##STR00514##
[4-(7- isopropoxy- 1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid cyclopentyl ester Mass (M +
H.sup.+): 441.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.38 (m,
6H), 1.53 (m, 2H), 1.65 (m, 6H), 1.79 (m, 4H), 3.03 (s, 3H), 3.24
(s, 3H), 3.72 (q, 2H), 4.64 (m, 1H), 4.89 (m, 1H), 5.07 (t, 1H),
6.52 (t, 1H), 6.84 (d, 1H), 7.25 (s, 1H) 7.82 (d, 2H). Example 454
##STR00515## 2-chloro-N- [4-(7- isopropoxy- 1-methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 467.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.26 (d, 6H), 1.58 (m, 2H), 1.72 (m, 2H), 2.94 (s, 3H), 3.27
(q, 2H), 3.54 (q, 2H), 4.68 (m, 1H), 6.83 (d, 1H), 7.04 (s, 1H),
7.41 (m, 4H), 7.94 (d, 1H), 8.09 (t, 1H), 8.37 (t, 1H).
<Preparative Example 27> Preparation of
[4-(3-hydrazino-7-methoxy-5-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00516##
[1476]
[4-(3-hydrazino-7-methoxy-5-methyl-quinoxaline-2-ylamino)-butyl]-ca-
rbamic acid-tert-butylester, a target compound of Preparative
Example 27, was obtained by the same manner as described in
Preparative Example 20.
Step 1: Preparation of
[4-(3-chloro-7-methoxy-5-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1477] Mass (M+H.sup.+): 395.1
[1478] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.33 (s, 9H), 1.40
(m, 2H), 1.57 (m, 2H), 2.46 (s, 3H), 2.92 (q, 2H), 3.41 (q, 2H),
3.80 (s, 3H), 6.75 (t, 1H), 6.81 (s, 1H), 6.83 (s, 1H), 7.27 (t,
1H).
Step 2: Preparation of
[4-(3-hydrazino-7-methoxy-5-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1479] Mass (M+H.sup.+): 391.2 Examples of the compounds
synthesized using
[4-(3-hydrazino-7-methoxy-5-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester prepared in step 1 of Preparative Example 27
are shown in Table 29 below.
TABLE-US-00029 TABLE 29 Example Structure Name Data Example 455
##STR00517## [4-(7- methoxy-1,9- dimethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- butylester
Mass (M + H.sup.+): 415.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.31 (s, 9H), 1.42 (m, 2H), 1.59 (m, 2H), 2.50 (s, 3H), 2.74
(s, 3H), 2.92 (q, 2H), 3.48 (q, 2H), 3.82 (s, 3H), 6.67 (s, 1H),
6.75 (t, 1H), 6.88 (s, 1H), 8.05 (t, 1H). Example 456 ##STR00518##
N.sup.1-(7- methoxy-1,9- dimethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-yl)- butane-1,4- diamine ditrifluoroacetic Mass (M
+ H.sup.+): 315.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.58 (m,
2H), 1.67 (m, 2H), 2.46 (s, 3H), 2.75 (s, 3H), 2.80 (m, 2H), 3.52
(q, 2H), 3.78 (s, 3H), acid 6.72 (s, 1H), 6.89 (s, 1H), 7.63 (brm,
2H), 8.25 (brm, 1H). Example 457 ##STR00519## [4-(7- methoxy-1,9-
dimethyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
carbamic acid- isopropylester Mass (M + H.sup.+): 400.47; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.10 (d, 6H), 1.43 (m, 2H), 1.59 (m,
2H), 2.50 (s, 3H), 2.74 (s, 3H), 2.95 (q, 2H), 3.47 (q, 2H), 3.77
(s, 3H), 4.68 (m, 1H), 6.68 (s, 1H), 6.88 (s, 1H), 6.94 (t, 1H),
8.05 (t, 1H). Example 458 ##STR00520## [4-(7- methoxy-1,9-
dimethyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-3-
methyl- butyramide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.81 (d, 6H), 1.44 (m, 2H), 1.60 (m, 2H), 1.86 (d,
2H), 1.87 (m, 1H), 2.48 (s, 3H), 2.74 (s, 3H), 3.04 (q, 2H), 3.47
(q, 2H), 3.82 (s, 3H), 6.68 (s, 1H), 6.87 (s, 1H), 7.69 (t, 1H),
8.06 (t, 1H).
<Preparative Example 28> Preparation of
[4-(8-chloro-3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00521##
[1481]
[4-(8-chloro-3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-ca-
rbamic acid-tert-butylester, a target compound of Preparative
Example 28, was obtained by the same manner as described in
Preparative Example 20.
Step 1: Preparation of 2,3,5-trichloro-6-methoxy-quinoxaline
[1482] (M+H.sup.+): 262.9
[1483] .sup.1H NMR (500 MHz, DMSO-d6) .delta.4.06 (s, 3H), 7.92 (d,
1H), 8.04 (d, 1H).
Step 2: Preparation of
[4-(3,8-dichloro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1484] (M+H.sup.+): 415.1
[1485] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.42 (s, 3H), 1.62
(m, 2H), 1.76 (m, 2H), 3.19 (m, 2H), 3.65 (m, 2H), 4.01 (s, 3H),
4.65 (s, 1H), 5.76 (s, 1H), 7.10 (d, 1H), 7.65 (d, 1H).
Step 3: Preparation of
[4-(8-chloro-3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1486] (M+H.sup.+): 411.2
[1487] Examples of the compounds synthesized using
[4-(8-chloro-3-hydrazino-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester prepared in step 3 of Preparative Example 28
are shown in Table 30 below.
TABLE-US-00030 TABLE 30 Example Structure Name Data Example 459
##STR00522## [4-(6- chloro-7- methoxy-1- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 435.2; .sup.1HNMR (500
MHz, DMSO-d6): .delta.1.30 (m, 9H), 1.43 (m, 2H), 1.65 (m, 2H),
2.93 (m, 5H), 3.54 (m, 2H), 3.88 (s, 3H), 6.72 (s, 1H), 7.01 (d,
1H), 7.93 (d, 1H), 8.38 (s, 1H) Example 460 ##STR00523## [4-(6-
chloro-7- methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-yl)-
butane-1,4- diamine dihydrochloride Mass (M + H.sup.+): 335.1;
.sup.1HNMR (500 MHz, DMSO-d6): .delta.1.62 (m, 2H), 1.72 (m, 2H),
2.82 (m, 2H), 2.97 (s, 3H), 3.58 (d, 2H), 3.89 (s, 3H), 7.05 (d,
1H), 7.95 (m, 4H), 8.48 (s, 1H) Example 461 ##STR00524## [4-(6-
chloro-7- methoxy-1- methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-3- methyl- butyramide Mass (M + H.sup.+): 419.2;
.sup.1HNMR (500 MHz, DMSO-d6): .delta.0.78 (m, 6H), 1.44 (m, 2H),
1.65 (m, 2H), 1.86 (m, 3H), 2.96 (s, 3H), 3.28 (m, 2H), 3.56 (m,
2H), 3.89 (s, 3H), 7.04 (d, 1H), 7.67 (s, 1H), 7.95 (d, 1H), 8.39
(t, 1H) Example 462 ##STR00525## [4-(6- chloro-7- methoxy-1-
methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
carbamic acid isobutylester Mass (M + H.sup.+): 459.1; .sup.1HNMR
(500 MHz, DMSO-d6): .delta.1.46 (m, 2H), 1.66 (m, 2H), 2.95 (s,
3H), 3.07 (m, 2H), 3.55 (m, 4H), 3.89 (m, 3H), 6.82 (s, 1H), 6.83
(m, 1H), 7.05 (d, 1H), 8.40 (t, 1H) Example 463 ##STR00526##
N-[4-(6- chloro-7- methoxy-1- methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-2- thiophene- 2-yl- acetamide
Mass (M + H.sup.+): 435.2; .sup.1HNMR (500 MHz, DMSO-d6):
.delta.0.80 (m, 6H), 1.45 (m, 2H), 1.65 (m, 2H), 1.67 (m, 1H), 2.95
(m, 5H), 3.57 (m, 2H), 3.65 (m, 2H), 3.88 (s, 3H), 7.01 (m, 2H),
7.92 (d, 1H), 8.40 (t, 1H)
<Preparative Example 29>[Preparation of
4-(3-hydrazino-7-methoxy-6-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00527##
[1489]
[4-(3-Hydrazino-7-methoxy-6-methyl-quinoxaline-2-ylamino)-butyl]-ca-
rbamic acid-tert-butylester, a target compound of Preparative
Example 20, was obtained by the same manner as described in
Preparative Example 20 using
2,3-dichloro-6-methoxy-7-methyl-quinoxaline prepared in step 1 of
Preparative Example 11.
Step 1: Preparation of
[4-(3-chloro-7-methoxy-6-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1490] Mass (M+H.sup.+): 395.1
[1491] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.33 (s, 9H), 1.40 (m,
2H), 1.55 (m, 2H), 2.21 (s, 3H), 2.92 (q, 2H), 3.39 (q, 2H), 3.87
(s, 3H), 6.74 (t, 1H), 6.96 (s, 1H), 7.19 (t, 1H), 7.44 (s,
1H).
Step 2: Preparation of
[4-(3-hydrazino-7-methoxy-6-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1492] Mass (M+H.sup.+): 391.2
<Example 464> Preparation of
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester
##STR00528##
[1494] 1.1 g of a target compound was obtained (86% yield) by the
same manner as described in step 2 of Preparative Example 1, except
that
[4-(3-hydrazino-7-methoxy-6-methyl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (1.2 g, 3.1 mmol) prepared in step 2 of
Preparative Example 29 was used.
[1495] Mass (M+H.sup.+): 415.2
[1496] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.60 (m, 2H), 2.24 (s, 3H), 2.90 (q, 2H), 2.96 (s, 3H), 3.48
(q, 2H), 3.84 (s, 3H), 6.75 (t, 1H), 7.05 (s, 1H), 7.80 (s, 1H),
7.90 (t, 1H).
<Example 465> Preparation of
N.sup.1-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid
##STR00529##
[1498] 0.91 g of a target compound was obtained (70% yield) by the
same manner as described in Example 58, except that
[4-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester (1.0 g, 2.4 mmol) prepared in
Example 464 was used.
[1499] Mass (M+H.sup.+): 315.1
[1500] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.60 (m, 2H), 1.69
(m, 2H), 2.25 (s, 3H), 2.82 (m, 2H), 2.98 (s, 3H), 3.53 (q, 2H),
3.84 (s, 3H), 7.04 (s, 1H), 7.63 (brm, 3H), 7.83 (s, 1H), 8.07
(brm, 1H).
<Example 466> Preparation of
N-[4-(7-methoxy-1,8-dimethyl-[-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide
##STR00530##
[1502] 62 mg of a target compound was obtained (70% yield) by the
same manner as described in Example 59, except that
N.sup.1-(7-methoxy-1,8-dimethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)-b-
utane-1,4-diamine ditrifluoroacetic acid (120 mg, 0.22 mmol)
prepared in Example 465 was used.
[1503] Mass (M+H.sup.+): 399.2
[1504] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.02 (s, 9H), 1.45 (m,
2H), 1.60 (m, 2H), 2.24 (s, 3H), 2.97 (s, 3H), 3.04 (q, 2H), 3.49
(q, 2H), 3.84 (s, 3H), 7.04 (s, 1H), 7.37 (t, 1H), 7.81 (s, 1H),
7.94 (t, 1H).
[1505] The compounds shown in Table 31 below were prepared by the
same manner as described in Example 466.
TABLE-US-00031 TABLE 31 Example Structure Name Data Example 467
##STR00531## [4-(7- methoxy- 1,8- dimethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isopropylester
Mass (M + H.sup.+): 401.1; .sup.1HNMR (500 MHz, DMSO-d6):
.delta.1.09 (d, 6H), 1.45 (m, 2H), 1.61 (m, 2H), 2.24 (s, 3H), 2.96
(s, 3H + m, 2H), 3.49 (q, 2H), 3.84 (s, 3H), 4.68 (m, 1H), 6.95 (t,
1H), 7.05 (s, 1H), 7.80 (s, 1H), 7.94 (t, 1H). Example 468
##STR00532## [4-(7- methoxy- 1,8- dimethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 415.1; .sup.1HNMR (500 MHz, DMSO-d6): .delta.0.81
(d, 6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.76 (m, 1H), 2.97 (s, 3H),
2.98 (m, 2H), 3.48 (q, 2H), 3.66 (q, 2H), 3.84 (s, 3H), 7.04 (s +
t, 2H), 7.81 (s, 1H), 7.94 (t, 1H). Example 469 ##STR00533##
N-[4-(7- methoxy- 1,8- dimethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-3- methyl- butyramide Mass (M +
H.sup.+): 399.2; .sup.1HNMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.44 (m, 2H), 1.61 (m, 2H), 1.87 (d, 2H), 1.90 (m, 1H), 2.24
(s, 3H), 2.96 (s, 3H), 3.04 (q, 2H), 3.48 (q, 2H), 3.84 (s, 3H),
7.04 (s, 1H), 7.70 (t, 1H), 7.80 (s, 1H), 7.94 (t, 1H). Example 470
##STR00534## 2-chloro-N- [4-(7- methoxy- (1,8- dimethyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- benzamide
Mass (M + H.sup.+): 453.2; .sup.1HNMR (500 MHz, DMSO-d6):
.delta.1.57 (brm, 2H), 1.72 (brm, 2H), 2.24 (s, 3H), 2.97 (s, 3H),
3.26 (q, 2H), 3.52 (m, 2H), 3.83 (s, 3H), 7.05 (s, 1H), 7.32 (m,
3H), 7.41 (m, 1H), 7.80 (s, 1H), 7.97 (t, 1H), 8.36 (t, 1H).
<Preparative Example 30> Preparation of
[4-(3-hydrazino-7-methoxy-6-trifluoromethyl-quinoxaline-2-ylamino)-butyl]-
-carbamic acid-tert-butylester
##STR00535##
[1507]
[4-(3-Hydrazino-7-methoxy-6-trifluoromethyl-quinoxaline-2-ylamino)--
butyl]-carbamic acid-tert-butylester, a target compound of
Preparative Example 30, was obtained by the same manner as
described in Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-methoxy-7-trifluoromethyl-quinoxaline
[1508] .sup.1H NMR (500 MHz, DMSO-d6): .delta.4.04 (s, 3H), 7.75
(s, 1H), 8.37 (s, 1H).
Step 2: Preparation of
[4-(3-chloro-7-methoxy-6-trifluoromethyl-quinoxaline-2-ylamino)-butyl]-ca-
rbamic acid tert-butylester
[1509] Mass (M+H.sup.+): 449.1
[1510] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.40 (m,
2H), 1.58 (m, 2H), 2.91 (q, 2H), 3.44 (m, 2H), 3.95 (s, 3H), 6.74
(t, 1H), 7.17 (s, 1H), 7.79 (t, 1H), 7.90 (s, 1H)
Step 3: Preparation of
[4-(3-hydrazino-7-methoxy-6-trifluoromethyl-quinoxaline-2-ylamino)-butyl]-
-carbamic acid-tert-butylester
[1511] Mass (M+H.sup.+): 445.1
[1512] Examples of the compounds synthesized using
[4-(3-hydrazino-7-methoxy-6-trifluoromethyl-quinoxaline-2-ylamino)-butyl]-
-carbamic acid-tert-butylester prepared in step 3 of Preparative
Example 30 are shown in Table 32 below.
TABLE-US-00032 TABLE 32 Example Structure Name Data Example 471
##STR00536## [4-(7- methoxy-1- methyl-8- trifluoromethyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid-tert- Mass (M + H.sup.+): 469.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.32 (s, 9H), 1.44 (m, 2H), 1.62 (m, 2H), 2.92 (q,
2H), 2.98 (s, 3H), 3.53 (q, 2H), 3.93 (s, 3H), 6.75 (t, 1H), 7.26
(s, 1H), 8.09 (s, butylester 1H), 8.56 (t, 1H). Example 472
##STR00537## N.sup.1-(7- methoxy-1- methyl-8- trifluoromethyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-yl)-butane-1,4- diamine
ditrifluoro Mass (M + H.sup.+): 369.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.59 (m, 2H), 1.70 (m, 2H), 2.82 (m, 2H), 2.99 (s,
3H), 3.57 (q, 2H), 3.93 (s, 3H), 7.24 (s, 1H), 7.61 (brm, 2H),
acetic acid 8.11 (s, 1H), 8.61 (t, 1H). Example 473 ##STR00538##
[4-(7- methoxy-1- methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isopropylester
Mass (M + H.sup.+): 455.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.10 (d, 6H), 1.45 (m, 2H), 1.62 (m, 2H), 2.96 (m, 2H), 2.99
(s, 3H), 3.54 (q, 2H), 3.93 (s, 3H), 4.68 (m, 1H), 6.96 (t, 1H),
7.26 (s, 1H), 8.09 (s, 1H), 8.56 (t, 1H). Example 474 ##STR00539##
[4-(7- methoxy-1- methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 469.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81
(d, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.76 (m, 1H), 2.97 (m, 2H),
2.99 (s, 3H), 3.53 (q, 2H), 3.65 (d, 2H), 3.93 (s, 3H), 7.03 (t,
1H), 7.26 (s, 1H), 8.09 (s, 1H), 8.56 (t, 1H). Example 475
##STR00540## [4-(7- methoxy-1- methyl-8- trifluoromethyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid cyclopentyl ester Mass (M + H.sup.+): 481.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.38~1.55 (m, 8H), 1.62 (m, 2H), 1.73 (m,
2H), 2.95 (m, 2H), 2.98 (s, 1H), 3.53 (q, 2H), 3.93 (s, 3H), 4.68
(m, 2H), 6.94 (t, 1H), 7.25 (s, 1H), 8.08 (s, 1H), 8.56 (t, 1H).
Example 476 ##STR00541## N-[4-(7- methoxy-1- methyl-8-
trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]-3- methyl- butyramide Mass (M + H.sup.+): 453.3; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44 (m, 2H), 1.64 (m,
2H), 1.87 (d, 2H), 1.89 (m, 1H), 2.98 (s, 3H), 3.05 (q, 2H), 3.53
(q, 2H), 3.93 (s, 3H), 7.26 (s, 1H), 7.70 (t, 1H), 8.09 (s, 1H),
8.57 (t, 1H). Example 477 ##STR00542## N-[4-(7- methoxy-1-
methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-2,2- dimethyl- propionamide Mass (M + H.sup.+):
453.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.02 (s, 9H), 1.45
(m, 2H), 1.62 (m, 2H), 2.98 (s, 3H), 3.04 (q, 2H), 3.53 (q, 2H),
3.93 (s, 3H), 7.25 (s, 1H), 7.38 (t, 1H), 8.09 (s, 1H), 8.56 (t,
1H). Example 478 ##STR00543## 2-(R)- hydroxy-N- [4-(7- methoxy-1-
methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-3- methyl- Mass (M + H.sup.+): 469.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.47 (m,
2H), 1.63 (m, 2H), 1.91 (m, 1H), 2.97 (s, 3H), 3.06 (m, 1H), 3.13
(m, 1H), 3.53 (q, 2H), 3.60 (t, 1H), 3.93 (s, 3H), butyramide 5.24
(d, 1H), 7.25 (s, 1H), 7.65 (t, 1H), 8.58 (t, 1H). Example 479
##STR00544## 2-(S)- hydroxy-N- [4-(7- methoxy-1- methyl-8-
trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]-3- methyl- Mass (M + H.sup.+): 469.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.47 (m, 2H), 1.63 (m,
2H), 1.91 (m, 1H), 2.97 (s, 3H), 3.06 (m, 1H), 3.13 (m, 1H), 3.53
(q, 2H), 3.60 (t, 1H), 3.93 (s, 3H), butyramide 5.24 (d, 1H), 7.25
(s, 1H), 7.65 (t, 1H), 8.58 (t, 1H). Example 480 ##STR00545##
N-[4-(7- methoxy-1- methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]-2- thiophene- 2-yl- acetamide
Mass (M + H.sup.+): 493.1; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.47 (m, 2H), 1.64 (m, 2H), 2.98 (s, 3H), 3.08 (q, 2H), 3.54
(q, 2H), 3.56 (s, 2H), 3.92 (s, 3H), 6.83 (s, 1H), 6.87 (d, 1H),
7.26 (s + d, 2H), 8.02 (t, 1H), 8.90 (s, 1H), 8.57 (t, 1H). Example
481 ##STR00546## 2-chloro-N- [4-(7- methoxy-1- methyl-8-
trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]- benzamide Mass (M + H.sup.+): 507.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.57 (m, 2H), 1.73 (m, 2H), 2.98 (s, 3H), 3.23 (q,
2H), 3.25 (s, 3H), 3.58 (q, 2H), 3.92 (s, 3H), 7.27 (s, 1H),
7.29~7.42 (m, 4H), 8.10 (s, 2H), 8.36 (t, 1H), 8.60 (t, 1H).
Example 482 ##STR00547## 1- cyclohexyl- 3-[4-(7- methoxy-1-
methyl-8- trifluoromethyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]-urea Mass (M + H.sup.+): 494.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.98 (m, 2H), 1.04 (m, 1H), 1.18 (m, 2H),
1.40 (m, 2H), 1.49 (m, 2H), 1.54 (m, 2H), 1.62 (m, 2H), 1.69 (m,
2H), 2.96 (m, 2H), 2.98 (s, 3H), 3.54 (q, 2H), 3.93 (s, 3H), 5.59
(d, 1H), 5.64 (t, 1H), 7.27 (s, 1H), 8.09 (s, 1H), 8.57 (t,
1H).
<Preparative Example 31> Preparation of
4-chloro-7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline
##STR00548##
[1514]
4-Chloro-8-methoxy-7-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,-
3-a]quinoxaline, a target compound of Preparative Example 31, was
obtained by the same manner as described in Preparative Example
5.
Step 1: Preparation of
2,3-chloro-6-methoxy-7-(2-methoxy-ethoxy)-quinoxaline
[1515] Mass (M+H.sup.+): 267.0
[1516] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.27 (s, 3H), 3.61 (t,
2H), 3.69 (s, 3H), 3.95 (t, 2H), 6.69 (s, 2H), 11.66 (s, 1H), 11.67
(s, 1H).
Step 2: Preparation of
[3-chloro-6-methoxy-7-(2-methoxy-ethoxy)-quinoxaline-2-yl]-hydrazine
[1517] Mass (M+H.sup.+): 303.0
[1518] .sup.1H NMR (500 MHz, DMSO-d6) .delta.3.30 (s, 3H), 3.71 (t,
2H), 3.95 (s, 3H), 4.28 (t, 2H), 7.42 (s, 1H), 7.44 (s, 1H).
Step 3: Preparation of
4-chloro-7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline
[1519] Mass (M+H.sup.+): 323.1
[1520] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.13 (s, 3H), 3.28
(s, 3H), 3.68 (t, 2H), 4.00 (s, 3H), 4.21 (t, 2H), 7.50 (s, 1H),
7.64 (s, 1H).
<Example 483> Preparation of
{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00549##
[1522] 0.17 g of a target compound was obtained (26% yield) by the
same manner as described in Example 57, except that
4-chloro-7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline prepared in step 3 of Preparative Example 31 was
used.
[1523] Mass (M+H.sup.+): 475.2
[1524] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.42 (m,
2H), 1.60 (m, 2H), 2.92 (q, 2H), 3.01 (s, 3H), 3.31 (s, 3H), 3.47
(q, 2H), 3.68 (t, 2H), 3.83 (s, 3H), 4.20 (t, 2H), 6.75 (t, 1H),
7.09 (s, 1H), 7.54 (s, 1H), 7.80 (t, 1H)
<Example 484> Preparation of
N.sup.1-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00550##
[1526] 0.13 g of a target compound was obtained (84% yield) by the
same manner as described in Example 58, except that
{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester prepared in
Example 483 was used.
[1527] Mass (M+H.sup.+): 375.0
[1528] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.68
(m, 2H), 2.82 (m, 2H), 3.31 (s, 3H), 3.52 (q, 2H), 3.69 (t, 2H),
3.83 (s, 3H), 4.21 (t, 2H), 7.09 (s, 1H), 7.57 (s, 1H), 7.63 (brm,
2H), 7.94 (brs, 1H)
<Example 485> Preparation of
N-{4-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide
##STR00551##
[1530] 0.05 g of a target compound was obtained (81% yield) by the
same manner as described in Example 65, except that
N.sup.1-[7-methoxy-8-(2-methoxy-ethoxy)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid prepared
in Example 484 was used.
[1531] Mass (M+H.sup.+): 459.2
[1532] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.45 (m,
2H), 1.62 (m, 2H), 1.86 (m, 2H), 1.91 (m, 1H), 3.01 (s, 3H), 3.04
(m, 2H), 3.31 (s, 3H), 3.47 (q, 2H), 3.68 (t, 2H), 3.83 (s, 3H),
4.21 (t, 2H), 7.10 (s, 1H), 7.56 (s, 1H), 7.70 (t, 1H), 7.82 (t,
1H).
<Preparative Example 32> Preparation of
[4-(3-hydrazino-5,6,7-trimethoxy-quinoxaline-2-ylamino)butyl]-carbamic
acid-tert-butyl ester
##STR00552##
[1534]
[4-(3-Hydrazino-5,6,7-trimethoxy-quinoxaline-2-ylamino)butyl]-carba-
mic acid-tert-butyl ester, a target compound of Preparative Example
32, was obtained by the same manner as described in Preparative
Example 20.
Step 1: Preparation of
[4-(3-chloro-5,6,7-trimethoxy-quinoxaline-2-ylamino)-butyl]carbamic
acid-tert-butylester
[1535] Mass (M+H.sup.+): 441.1
[1536] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.40
(m, 2H), 1.56 (m, 2H), 2.91 (m, 2H), 3.40 (m, 2H), 3.75 (s, 3H),
3.87 (s, 3H), 3.94 (s, 3H), 6.73 (t, 1H), 6.82 (s, 1H), 7.23 (t,
1H).
Step 2: Preparation of
{4-[(3-hydrazino-7,8,9-trimethoxy)-quinoxaline-2-ylamino]butyl]carbamic
acid-tert-butylester
[1537] Mass (M+H.sup.+): 437.1
<Example 486> Preparation of
[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester
##STR00553##
[1539] 0.32 g of a target compound was obtained (94% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
{4-[(3-hydrazino-7,8,9-trimethoxy)-quinoxaline-2-ylamino]butyl}carbamic
acid-tert-butylester prepared in step 2 of Preparative Example 32
was used.
[1540] Mass (M+H.sup.+): 461.2
[1541] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.43 (m,
2H), 1.59 (m, 2H), 2.83 (s, 3H), 2.93 (m, 2H), 3.47 (m, 2H), 3.79
(s, 3H), 3.82 (s, 3H), 3.86 (s, 3H), 6.74 (t, 1H), 6.91 (s, 1H),
7.95 (t, 1H).
<Example 487> Preparation of
N.sup.1-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid
##STR00554##
[1543] 0.35 g of a target compound was obtained (97% yield) by the
same manner as described in Example 58, except that
[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino-
)-butyl]-carbamic acid-tert-butylester prepared in Example 486 was
used.
[1544] Mass (M+H.sup.+): 361.2
<Example 488> Preparation of
3-methyl-N-[4-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-ylamino)-butyl]-butyramide
##STR00555##
[1546] 0.08 g of a target compound was obtained (52% yield) by the
same manner as described in Example 37, except that
N.sup.1-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid prepared in Example 487
was used.
[1547] Mass (M+H.sup.+): 445.2
[1548] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.45
(m, 2H), 1.63 (m, 2H), 1.85 (m, 2H), 1.87 (m, 1H), 2.83 (s, 3H),
2.92 (q, 2H), 3.47 (m, 2H), 3.79 (s, 3H), 3.82 (s, 3H), 3.85 (s,
3H), 6.74 (t, 1H), 6.91 (s, 1H), 7.94 (t, 1H)
<Example 489>3-methyl-pentanoic
acid-[4-(6,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino)-butyl]-amide
##STR00556##
[1550] 0.11 g of a target compound was obtained (68% yield) by the
same manner as described in Example 73, except that
N.sup.1-(7,8,9-trimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
)-butane-1,4-diamine ditrifluoroacetic acid prepared in Example 487
was used.
[1551] Mass (M+H.sup.+): 459.2
[1552] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.76 (m, 6H),
1.08-1.20 (brm, 2H), 1.45 (m, 2H), 1.62 (m, 2H), 1.78 (m, 2H), 1.98
(m, 1H), 2.83 (s, 3H), 2.92 (q, 2H), 3.47 (m, 2H), 3.78 (s, 3H),
3.82 (s, 3H), 3.85 (s, 3H), 6.74 (t, 1H), 6.91 (s, 1H), 7.94 (t,
1H).
<Preparative Example 33> Preparation of
[4-(3-hydrazino-7-imidazole-1-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00557##
[1554]
[4-(3-Hydrazino-7-imidazole-1-yl-quinoxaline-2-ylamino)-butyl]-carb-
amic acid-tert-butylester, a target compound of Preparative Example
33, was obtained by the same manner as described in Preparative
Example 20.
Step 1: Preparation of
2,3-dichloro-6-imidazole-1-yl-quinoxaline
[1555] Mass (M+H.sup.+): 265.1
[1556] .sup.1H NMR (500 MHz, DMSO-d6) .delta.7.16 (s, 1H), 8.02 (s,
1H), 8.16 (d, 1H), 8.30 (d, 1H), 8.39 (d, 1H), 8.55 (s, 1H).
Step 2: Preparation of
[4-(3-chloro-7-imidazole-1-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1557] Mass (M+H.sup.+): 417.1
[1558] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.31 (s, 9H), 1.42 (m,
2H), 1.60 (m, 2H), 2.91 (m, 2H), 3.43 (m, 2H), 6.75 (s, 1H), 7.10
(s, 1H), 7.76 (m, 1H), 7.77 (m, 1H), 7.80 (m, 2H), 7.92 (m, 1H),
8.42 (s, 1H).
Step 3: Preparation of
[4-(3-hydrazino-7-imidazole-1-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1559] Mass (M+H.sup.+): 413.2 Examples of the compounds
synthesized using
[4-(3-hydrazino-7-imidazole-1-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester prepared in step 3 of Preparative Example 33
are shown in Table 33 below.
TABLE-US-00033 TABLE 33 Example Structure Name Data Example 490
##STR00558## [4-(7- imidazole- 1-yl-1- methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- butylester
Mass (M + H.sup.+): 437.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.31 (m, 9H), 1.44 (m, 2H), 1.63 (m, 2H), 2.93 (m, 2H), 3.00
(s, 3H) 3.52 (m, 2H), 6.80 (s, 1H), 7.10 (s, 1H), 7.54 (d, 1H),
7.80 (s, 1H), 7.86 (s, 1H), 8.11 (d, 1H), 8.32 (m, 1H), 8.36 (s,
1H). Example 491 ##STR00559## N.sup.1-(7- imidazole- 1-yl-1-
methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-yl)- butane-1,4-
diamine dihydrochloride Mass (M + H.sup.+): 337.1; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.65 (m, 2H), 1.72 (m, 2H), 2.80 (m, 2H),
3.04 (s, 3H), 3.59 (m, 2H), 7.70 (d, 1H), 7.93 (s, 1H), 8.05 (s,
2H), 8.10 (s, 3H), 8.23 (d, 1H), 8.42 (s, 1H), 8.72 (s, 1H), 9.90
(s, 1H) Example 492 ##STR00560## N-[4-(7- imidazole- 1-yl-1-
methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-
3-methyl- butyramide Mass (M + H.sup.+): 421.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.78 (m, 6H), 1.46 (m, 2H), 1.63 (m, 2H),
1.87 (m, 3H), 3.01 (s, 3H) 3.04 (m, 2H), 3.53 (m, 2H), 7.12 (s,
1H), 7.56 (d, 1H), 7.72 (s, 1H), 7.81 (s, 1H), 7.88 (s, 1H), 8.12
(d, 1H), 8.32 (s, 1H), 8.41 (s, 1H). Example 493 ##STR00561## 4-(7-
imidazole- 1-yl-1- methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid isobutylester Mass (M + H.sup.+):
437.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (t, 6H), 1.46
(m, 2H), 1.63 (m, 2H), 1.75 (m, 1H), 2.98 (m, 5H), 3.53 (m, 2H),
3.66 (m, 2H), 7.03 (s, 1H), 7.11 (s, 1H), 7.54 (d, 1H), 7.80 (s,
1H), 7.87 (s, 1H), 8.11 (d, 1H), 8.13 (s, 1H), 8.38 (s, 1H).
Example 494 ##STR00562## [4-(7- imidazole- 1-yl-1- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid isopropylester Mass (M + H.sup.+): 423.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.08 (t, 6H), 1.45 (m, 2H), 1.64 (m, 2H),
2.97 (m, 2H), 3.01 (s, 3H), 3.55 (m, 2H), 6.95 (s, 1H), 7.23 (s,
1H), 7.55 (d, 1H), 7.84 (s, 1H), 7.95 (s, 1H), 8.14 (d, 1H), 8.34
(s, 1H), 8.60 (s, 1H). Example 495 ##STR00563## 3-methyl- pentanoic
acid-[4-(7- imidazole- 1-yl-1- methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- amide Mass (M + H.sup.+): 435.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.74 (m, 6H), 1.05 (m, 1H),
1.22 (m, 1H), 1.45 (m, 2H), 1.63 (m, 3H), 1.79 (m, 1H), 3.01 (s,
3H), 3.05 (m, 2H), 3.52 (m, 2H), 7.10 (s, 1H), 7.55 (d, 1H), 7.72
(s, 1H), 7.81 (s, 1H), 7.87 (s, 1H), 8.12 (d, 1H), 8.32 (s, 1H),
8.37 (s, 1H). Example 496 ##STR00564## N-[4-(7- imidazole- 1-yl-1-
methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-2-
thiophene- 2-yl- acetamide Mass (M + H.sup.+): 461.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.47 (m, 2H), 1.64 (m, 2H), 3.00 (s,
3H), 3.08 (m, 2H), 3.53 (m, 2H), 3.56 (s, 2H), 6.83 (m, 2H), 7.20
(s, 1H), 7.24 (d, 1H), 7.25 (d, 1H), 7.81 (d, 1H), 7.92 (s, 1H),
8.05 (m, 1H), 8.12 (d, 1H), 8.30 (m, 1H), 8.53 (s, 1H).
<Preparative Example 34> Preparation of
[4-(3-hydrazino-7-morpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00565##
[1561]
[4-(3-Hydrazino-7-morpholine-4-yl-quinoxaline-2-ylamino)-butyl]-car-
bamic acid-tert-butylester, a target compound of Preparative
Example 34, was obtained by the same manner as described in
Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-morpholine-4-yl-quinoxaline
[1562] Mass (M+H.sup.+): 284.0
[1563] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.37 (t, 4H), 3.74
(t, 4H), 7.19 (d, 1H), 7.76 (d, 1H), 7.84 (d, 1H).
Step 2: Preparation of
[4-(3-chloro-7-morpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1564] Mass (M+H.sup.+): 436.2
Step 3: Preparation of
[4-(2,3-hydrazino-7-morpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carbami-
c acid-tert-butylester
[1565] Mass (M+H.sup.+): 432.3
[1566] Examples of the compounds synthesized using
[4-(3-hydrazino-7-morpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester prepared in step 3 of Preparative Example 34
are shown in Table 34 below.
TABLE-US-00034 TABLE 34 Example Structure Name Data Example 497
##STR00566## [4-(1- methyl-7- morpholine- 4-yl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 456.3; .sup.1H NMR (500
Hz, DMSO-d6): .delta.1.32 (s, 9H), 1.42 (m, 2H), 1.61 (m, 2H), 2.93
(m, 5H), 3.14 (t, 4H), 3.50 (m, 2H), 3.72 (t, 4H), 6.75 (s, 1H),
6.91 (d, 1H), 7.00 (d, 1H), 7.87 (d, 1H), 7.97 (s, 1H). Example 498
##STR00567## N.sup.1-(1- methyl-7- morpholine-4-yl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-yl)- butane-1,4- diamine
dihydrochloride Mass (M + H.sup.+): 356.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.70 (m, 2H), 1.75 (m, 2H), 2.81 (m, 2H), 2.99 (s,
3H), 3.16 (m, 4H), 3.75 (m, 4H), 3.88 (m, 2H), 4.20 (s, 2H), 7.06
(d, 1H), 7.94 (d, 1H), 8.05 (s, 4H) Example 499 ##STR00568##
3-methyl-N- [4-(1- methyl-7- morpholine-4-yl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- butyramide Mass (M + H.sup.+):
440.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.43
(m, 2H), 1.61 (m, 2H), 1.88 (m, 3H), 2.93 (s, 3H), 3.04 (m, 2H),
3.14 (s, 4H), 3.49 (m, 2H), 3.73 (d, 4H), 6.90 (d, 2H), 7.00 (s,
1H), 7.86 (d, 1H), 8.00 (s, 1H) Example 500 ##STR00569## 2-(S)-
fluoro-3- methyl-N- [4-(1-methyl-7- morpholine- 4-yl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- butyramide
Mass (M + H.sup.+): 458.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.78 (m, 3H), 0.90 (m, 3H), 1.49 (m, 2H), 1.61 (m, 2H), 2.10
(m, 1H), 2.90 (s 3H), 3.10 (m, 6H), 3.49 (m, 2H), 3.73 (s, 4H),
4.56 (d, 1H), 6.90 (d, 1H), 7.00 (s, 1H), 7.86 (d, 1H), 8.08 (s,
1H). Example 501 ##STR00570## 3-methyl- pentanoic acid-[4-(1-
methyl-7- morpholine- 4-yl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- amide Mass (M + H.sup.+): 454.3; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.75 (m, 6H), 1.05 (m, 1H), 1.25 (m,
1H), 1.45 (m, 2H), 1.63 (m, 2H), 1.75 (m, 1H), 1.81 (m, 1H), 1.97
(m, 1H), 2.94 (s, 3H), 3.00 (m, 2H), 3.19 (m, 4H), 3.49 (m, 2H),
3.72 (m, 4H), 6.93 (d, 1H), 7.01 (s, 1H), 7.70 (m, 1H), 7.88 (d,
1H), 8.00 (s, 1H) Example 502 ##STR00571## (S)-{2-methyl-1-
[4-(1-methyl-7- morpholine- 4-yl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butylcarbamoyl]- propyl}-carbamic
acid-tert- butylester Mass (M + H.sup.+): 555.4; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.73 (m, 6H), 1.32 (m, 9H), 1.44 (m, 2H),
1.63 (m, 2H), 1.80 (m, 1H), 2.94 (s 3H), 3.12 (m, 1H), 3.15 (m,
5H), 3.49 (m, 2H), 3.67 (m, 1H), 3.73 (m, 4H), 6.48 (d, 1H), 6.91
(d, 1H), 7.01 (s, 1H), 7.79 (s, 1H), 7.88 (d, 1H), 8.00 (s, 1H).
Example 503 ##STR00572## 2-(S)-amino-3- methyl-N- [4-(1-methyl-7-
morpholine- 4-yl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)-
butyl]- butyramide hydrochloride Mass (M + H.sup.+): 455.3; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.86 (m, 6H), 1.57 (m, 2H), 1.72 (m,
2H), 2.03 (m, 1H), 3.00 (s, 3H), 3.16 (m, 6H), 3.15 (m, 5H), 3.55
(m, 1H), 3.75 (m, 4H), 3.85 (s, 2H), 7.08 (d, 1H), 6.95 (d, 1H),
8.21 (s, 3H), 8.67 (s, 1H). Example 504 ##STR00573## (S)-2-(2-(S)-
hydroxy- propionylamino)- 3-methyl-N- [4-(1-methyl-7- morpholine-
4-yl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- Mass
(M + H.sup.+): 527.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.77
(m, 6H), 1.17 (s, 3H), 1.49 (m, 2H), 1.66 (m, 2H), 1.95 (m, 1H),
3.00 (s, 3H), 3.15 (m, 6H), 3.55 (m, 2H), 3.75 (m, 4H), 3.90 (s,
butyramide 1H), 4.10 (d, 1H), hydrochloride 7.00 (d, 1H), 7.35 (d,
1H), 7.60 (s, 1H), 7.90 (d, 1H), 8.15 (m, 1H). Example 505
##STR00574## 2-(S)- methanesul- fonylamino- 3-methyl- N-[4-(1-
methyl-7- morphonyl- 4-yl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- Mass (M + H.sup.+): 533.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.79 (m, 6H), 1.47 (m, 2H), 1.63 (m, 2H),
1.81 (m, 1H), 2.74 (s, 3H), 2.94 (s, 3H), 3.15 (m, 6H), 3.55 (m,
3H), 3.72 (m, 4H), 6.90 (d, 1H), 7.00 (s, 1H), butyramide 7.10 (d,
1H), 7.89 (d, 1H), 8.00 (m, 2H). Example 506 ##STR00575## [4-(1-
methyl-7- morpholine- 4-yl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino)- butyl]- carbamic acid isopropylester Mass (M +
H.sup.+): 442.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.10 (d,
6H), 1.43 (m, 2H), 1.60 (m, 2H), 2.93 (s, 3H), 2.98 (m, 2H), 3.15
(s, 4H), 3.47 (m, 2H), 3.73 (s, 4H), 4.67 (m, 1H), 6.89 (d, 1H),
6.91 (s, 1H), 7.00 (s, 1H), 7.86 (d, 1H), 7.97 (s, 1H) Example 507
##STR00576## N-[4-(1- methyl-7- morpholine- 4-yl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino)- butyl]-2-
thiophene- 2-yl- acetamide Mass (M + H.sup.+): 480.2; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.46 (m, 2H), 1.62 (m, 2H), 1.88 (m,
3H), 2.94 (s, 3H), 3.13 (m, 2H), 3.15 (m, 4H), 3.50 (m, 2H), 3.57
(s, 2H), 3.73 (t, 4H), 6.84 (m, 4H), 7.00 (s, 1H), 7.25 (s, 1H),
7.87 (d, 1H), 7.98 (m, 1H), 8.05 (m, 1H)
<Preparative Example 35> Preparation of
{4-[3-hydrazino-7-(2,6-dimethyl-morpholine-4-yl)-quinoxaline-2-ylamino]-b-
utyl}-carbamic acid-tert-butylester
##STR00577##
[1568]
{4-[3-Hydrazino-7-(2,6-dimethyl-morpholine-4-yl)-quinoxaline-2-ylam-
ino]-butyl}-carbamic acid-tert-butylester, a target compound of
Preparative Example 35, was obtained by the same manner as
described in Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-(2,6-dimethyl-morpholine-4-yl)-quinoxaline
[1569] Mass (M+H.sup.+): 312.0
[1570] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.17 (t, 6H), 3.66 (m,
2H), 3.90 (d, 2H), 7.19 (s, 1H), 7.75 (m, 2H), 7.84 (m, 2H).
Step 2: Preparation of
{4-[3-chloro-7-(2,6-dimethyl-morpholine-4-yl)-quinoxaline-2-ylamino]-buty-
l}-carbamic acid-tert-butylester
[1571] Mass (M+H.sup.+): 464.2
[1572] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.13 (d, 6H), 1.32 (s,
9H), 1.40 (m, 2H), 1.56 (m, 2H), 2.30 (t, 2H), 2.91 (m, 2H), 3.39
(m, 2H), 3.70 (m, 2H), 3.74 (d, 2H), 6.82 (s, 1H), 6.83 (s, 1H),
7.17 (m, 2H), 7.49 (d, 1H).
Step 3: Preparation of
{4-[3-hydrazino-7-(2,6-dimethyl-morpholine-4-yl)-quinoxaline-2-ylamino]-b-
utyl}-carbamic acid-tert-butylester
[1573] Mass (M+H.sup.+): 484.3
[1574] Examples of the compounds synthesized using
{4-[3-hydrazino-7-(2,6-dimethyl-morpholine-4-yl)-quinoxaline-2-ylamino]-b-
utyl}-carbamic acid-tert-butylester prepared in step 3 of
Preparative Example 35 are shown in Table 35 below.
TABLE-US-00035 TABLE 35 Example Structure Name Data Example 508
##STR00578## {4-[7- (2,6-dimethyl- morphonyl-4- yl)-1-methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino]- butyl}- carbamic
acid-tert- butylester Mass (M + H.sup.+): 484.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.14 (m, 6H), 1.32 (s, 9H), 1.43 (m, 2H),
1.61 (m, 2H), 2.23 (m, 2H), 2.94 (m, 5H), 3.47 (m, 2H), 3.65 (m,
4H), 6.80 (s, 1H), 6.90 (d, 1H), 7.00 (s, 1H), 7.84 (d, 1H), 8.00
(m, 1H). Example 509 ##STR00579## N.sup.1-[7- (2,6-dimethyl-
morphonyl-4- yl)-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-yl]- butane-1,4- diamine ditrifluoroacetic acid Mass (M +
H.sup.+): 384.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.14 (m,
6H), 1.60 (m, 2H), 1.69 (m, 2H), 2.25 (m, 2H), 2.80 (m, 2H), 2.95
(s, 3H), 3.53 (m, 2H), 3.65 (m, 4H), 6.95 (d, 1H), 7.03 (s, 1H),
7.67 (d, 3H), 7.89 (d, 1H), 8.22 (s, 1H). Example 510 ##STR00580##
N-{4-[7- (2,6-dimethyl- morpholine- 4-yl)-1-methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-3- methyl-
butyramide Mass (M + H.sup.+): 468.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (m, 6H), 1.14 (m, 6H), 1.44 (m, 2H), 1.62 (m,
2H), 1.87 (m, 3H), 2.24 (t, 2H), 2.93 (s, 3H), 3.04 (m, 2H), 3.48
(m, 2H), 3.63 (m, 4H), 6.93 (d, 1H), 7.00 (d, 1H), 7.70 (m, 1H),
7.86 (d, 1H), 7.97 (d, 1H). Example 511 ##STR00581## N-{4-[7-
(2,6-dimethyl- morphonyl- 4-yl)-1-methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-2- (S)-fluoro- 3-methyl-
butyramide Mass (M + H.sup.+): 486.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.90 (m, 3H), 0.92 (m, 3H), 1.14 (m, 6H), 1.55 (m,
2H), 1.68 (m, 2H), 2.05 (m, 1H), 2.35 (t, 2H), 2.98 (s, 3H), 3.11
(m, 2H), 3.62 (m, 2H), 3.71 (m, 4H), 4.57 (m, 1H), 7.08 (d, 1H),
7.72 (s, 1H), 7.93 (d, 1H), 8.16 (m, 1H), 9.47 (s, 1H). Example 512
##STR00582## N-{4-[7- (2,6-dimethyl- morpholine- 4-yl)-1- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino]- butyl}-2-
(R)-hydroxy- 3-methyl- butyramide Mass (M + H.sup.+): 484.3;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (m, 3H), 0.84 (m, 3H),
1.14 (s, 6H), 1.47 (m, 2H), 1.62 (m, 2H), 1.92 (m, 1H), 2.24 (t,
2H), 2.93 (s, 3H), 3.04 (m, 2H), 3.28 (m, 2H), 3.68 (m, 6H), 5.23
(d, 1H), 6.93 (d, 1H), 7.01 (s, 1H), 7.65 (m, 1H), 7.85 (d, 1H),
7.98 (s, 1H). Example 513 ##STR00583## (S)-{2- methyl-1-[4-
(1-methyl-7- (2,6-dimethyl- morpholine-4-yl)- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino)- butylcarbamoyl]- propyl}- carbamic
acid-tert- butylester Mass (M + H.sup.+): 583.4; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.77 (m, 6H), 1.14 (m, 6H), 1.32 (s, 9H),
1.45 (m, 2H), 1.63 (m, 2H), 1.84 (m, 1H), 2.26 (t, 2H), 2.93 (s,
3H), 3.04 (m, 2H), 3.50 (m, 2H), 3.68 (m, 5H), 6.48 (d, 1H), 6.93
(d, 1H), 7.01 (d, 1H), 7.79 (m, 1H), 7.86 (d, 1H), 7.97 (m, 1H).
Example 514 ##STR00584## 2-(S)-amino- N-{4-[7- (2,6-dimethyl-
morpholine- 4-yl)-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino]- butyl}-3- methyl- butyramide hydrochloride Mass (M +
H.sup.+): 483.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.87 (m,
6H), 1.14 (m, 6H), 1.57 (m, 2H), 1.71 (m, 2H), 2.03 (m, 1H), 2.33
(t, 2H), 2.98 (s, 3H), 3.08 (m, 1H), 3.22 (m, 1H), 3.55 (m, 2H),
3.64 (m, 6H), 7.07 (d, 1H), 7.95 (s, 1H), 8.19 (s, 3H), 8.62 (s,
1H). Example 515 ##STR00585## (S)-(1-{4- [7-(2,6-dimethyl-
morpholine- 4-yl)-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino]- butylcarbamoyl}- 2-methyl- propyl)- carbamic acid
isobutylester Mass (M + H.sup.+): 584.4; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.77 (m, 12H), 1.14 (m, 6H), 1.45 (m, 2H), 1.63
(m, 2H), 1.84 (m, 2H), 2.26 (t, 2H), 2.93 (s, 3H), 3.08 (m, 2H),
3.55 (m, 2H), 3.69 (m, 7H), 6.92 (m, 2H), 7.01 (s, 1H), 7.84 (d,
2H), 7.88 (s, 1H). Example 516 ##STR00586## (S)-(1-{4-
[7-(2,6-dimethyl- morpholine- 4-yl)-1-methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino]- butylcarbamoyl}- 2-methyl- propyl)-
carbamic acid propylester Mass (M + H.sup.+): 570.4; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.0.77 (m, 9H), 1.14 (m, 6H), 1.45 (m,
4H), 1.63 (m, 2H), 1.84 (m, 1H), 2.26 (m, 2H), 2.93 (s, 3H), 3.10
(m, 2H), 3.49 (m, 2H), 3.63 (m, 5H), 3.80 (s, 2H), 6.91 (m, 2H),
7.01 (s, 1H), 7.84 (m, 2H), 8.00 (s, 1H). Example 517 ##STR00587##
(S)-N-(1-{4- [7-(2,6-dimethyl- morpholine- methyl-
[1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino]- butylcarbamoyl}-
2-methyl- propyl)-2- (S)-fluoro- 3-methyl- butyramide Mass (M +
H.sup.+): 585.4; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.77 (m,
12H), 1.15 (m, 6H), 1.46 (m, 2H), 1.63 (m, 2H), 2.00 (m, 3H), 2.24
(t, 2H), 2.93 (s, 3H), 3.08 (m, 2H), 3.48 (m, 2H), 3.65 (m, 4H),
4.12 (m, 1H), 4.65 (d, 1H), 6.93 (d, 2H), 7.00 (s, 1H), 7.62 (d,
1H), 7.86 (d, 1H), 7.87 (m, 1H), 8.04 (m, 1H). Example 518
##STR00588## (S)-N-{4-[7- (2,6-dimethyl- morpholine-
4-yl)-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline- 4-ylamino]-
butyl}-3- methyl-2-(3- methyl- butyrylamino)- butyramide Mass (M +
H.sup.+): 567.4; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (m,
12H), 1.15 (m, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.98 (m, 4H), 2.25
(t, 2H), 2.94 (s, 3H), 3.08 (m, 2H), 3.49 (m, 2H), 3.66 (m, 4H),
4.04 (m, 1H), 6.93 (d, 1H), 7.01 (s, 1H), 7.67 (d, 1H), 7.86 (d,
1H), 7.88 (m, 1H) Example 519 ##STR00589## (S)-N-{4-[7-
(2,6-dimethyl- morpholine- methyl- [1,2,4]triazolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}-2- (2,2-dimethyl-
propionylamino)- 3-methyl- butyramide Mass (M + H.sup.+): 567.4;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.75 (m, 6H), 1.05 (m, 9H),
1.14 (s, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.90 (m, 1H), 2.26 (t,
2H), 2.93 (s, 3H), 3.00 (m, 1H), 3.15 (m, 1H), 3.48 (m, 2H), 3.66
(m, 4H), 4.04 (t, 3H), 6.95 (m, 2H), 7.00 (s, 1H), 7.86 (d, 2H),
7.97 (m, 1H). Example 520 ##STR00590## (S)-(1-{4- [7-(2,6-dimethyl-
morpholine- 4-yl)-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-
4-ylamino]- butylcarbamoyl}- 2-methyl- propyl)- carbamic acid
isopropylester Mass (M + H.sup.+): 569.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.77 (m, 6H), 1.14 (m, 12H), 1.45 (m, 2H), 1.63
(m, 2H), 1.84 (m, 2H), 2.26 (t, 2H), 2.93 (s, 3H), 3.08 (m, 2H),
3.55 (m, 2H), 3.69 (m, 5H), 4.66 (m, 1H), 6.91 (d, 1H), 6.90 (d,
1H), 7.00 (s, 1H), 7.86 (s, 1H), 7.88 (d, 1H), 7.97 (m, 1H).
<Preparative Example 36> Preparation of
[4-(3-hydrazino-7-thiomorpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carba-
mic acid-tert-butylester
##STR00591##
[1576]
[4-(3-thiomorpholine-4-yl-quinoxalineinoxaline-2-ylamino)-butyl]-ca-
rbamic acid-tert-butylester, a target compound of Preparative Ex
ample 36, was obtained by the same manner as described in
Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-thiomorpholine-4-yl-quinoxaline
[1577] Mass (M+H.sup.+): 301.0
[1578] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.60 (m, 4H), 3.40
(m, 4H), 6.63 (s, 1H), 6.71 (d, 1H), 6.99 (d, 1H)
Step 2: Preparation of
[4-(3-chloro-7-thiomorpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester
[1579] Mass (M-H.sup.+): 451.0
[1580] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.39
(m, 4H), 1.65 (m, 4H), 2.91 (m, 4H), 3.41 (m, 4H), 6.75 (t, 1H),
7.02 (s, 1H), 7.30 (t, 1H), 7.51 (d, 1H), 7.60 (d, 1H).
Step 3: Preparation of
[4-(3-hydrazino-7-thiomorpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carba-
mic acid-tert-butylester
[1581] Mass (M+H.sup.+): 448.3
<Example 521> Preparation of
{[4-(1-methyl-7-thiomorpholine-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-carbamic acid-tert-butylester
##STR00592##
[1583] 0.14 g of a target compound was obtained (10% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(3-hydrazino-7-thiomorpholine-4-yl-quinoxaline-2-ylamino)-butyl]-carba-
mic acid-tert-butylester (1.3 g, 2.88 mmol) prepared in step 3 of
Preparative Example 36 was used.
[1584] Mass (M+H.sup.+): 472.2
[1585] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43
(m, 2H), 1.60 (m, 2H), 2.65 (m, 4H), 2.95 (q, 2H), 2.93 (s, 3H),
3.40 (q, 2H), 3.58 (m, 4H), 6.75 (t, 1H), 6.89 (d, 1H), 6.99 (s,
1H), 7.87 (d, 1H), 7.96 (t, 1H).
<Example 522> Preparation of
N.sup.1-(1-methyl-7-thiomorphonyl-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl)-butane-1,4-diamine ditrifluoroacetic acid
##STR00593##
[1587] 0.13 g of a target compound was obtained (76% yield) by the
same manner as described in Example 58, except that
{[4-(1-methyl-7-thiomorpholine-4-yl)-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino]-butyl}-carbamic acid-tert-butylester (0.14 g, 0.3 mmol)
prepared in Example 521 was used.
[1588] Mass (M+H.sup.+): 372.2
[1589] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.59 (m, 2H), 1.69
(m, 2H), 2.66 (m, 4H), 2.82 (q, 2H), 2.98 (s, 3H), 3.50 (q, 2H),
3.60 (m, 4H), 6.93 (d, 1H), 7.00 (d, 1H), 7.66 (brs, 3H), 7.90 (d,
1H), 8.21 (br, 1H).
<Example 523> Preparation of
3-methyl-N-[4-(1-methyl-7-thiomorpholine-4-yl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino)-butyl]-butyramide
##STR00594##
[1591] 35 mg of a target compound was obtained (64% yield) by the
same manner as described in Example 37, except that
N.sup.1-(1-methyl-7-thiomorphonyl-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl)-butane-1,4-diamine ditrifluoroacetic acid (70 mg, 0.12 mmol)
prepared in Example 522 was used.
[1592] Mass (M+H.sup.+): 456.2
[1593] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.43 (m,
2H), 1.62 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 2.66 (m, 4H), 2.93
(s, 3H), 3.05 (q, 2H), 3.38 (q, 2H), 3.58 (m, 4H), 6.88 (d, 1H),
6.99 (s, 1H), 7.69 (t, 1H), 7.88 (d, 1H), 7.98 (t, 1H).
[1594] The compounds shown in Table 36 below were prepared by the
same manner as described in Example 38, except that
N.sup.1-(1-methyl-7-thiomorphonyl-4-yl-[1,2,4]triazolo[4,3-a]quinoxaline--
4-yl)-butane-1,4-diamine ditrifluoroacetic acid prepared in Example
522 was used.
TABLE-US-00036 TABLE 36 Example Structure Name Data Example 524
##STR00595## N-[4-(7- thiomorphonyl- 4-yl-1-methyl-
[1,2,4]triazolo[4,3- a]quinoxaline-4- ylamino)- butyl]-2-
(R)-hydroxy- 3-methyl- butyramide Mass (M + H.sup.+): 472.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.69 (d, 3H), 0.83 (d, 3H),
1.46 (m, 2H), 1.61 (m, 2H), 1.91 (m, 1H), 2.66 (m, 4H), 2.93 (s,
3H), 3.12 (m, 2H), 3.40 (q, 2H), 3.59 (q, 1H), 3.60 (m, 4H), 5.22
(d, 1H), 6.90 (d, 1H), 6.99 (s, 1H), 7.65 (t, 1H), 7.89 (d, 1H),
7.98 (t, 1H). Example 525 ##STR00596## N-[4-(7- thiomorphonyl-
4-yl-1-methyl- [1,2,4]triazolo[4,3- a]quinoxaline-4- ylamino)-
butyl]-2- (S)-hydroxy- 3-methyl- butyramide Mass (M + H.sup.+):
472.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.69 (d, 3H), 0.83
(d, 3H), 1.46 (m, 2H), 1.61 (m, 2H), 1.91 (m, 1H), 2.66 (m, 4H),
2.93 (s, 3H), 3.12 (m, 2H), 3.40 (q, 2H), 3.59 (q, 1H), 3.60 (m,
4H), 5.22 (d, 1H), 6.90 (d, 1H), 6.99 (s, 1H), 7.65 (t, 1H), 7.89
(d, 1H), 7.98 (t, 1H).
<Preparative Example 37> Preparation of
{4-[3-hydrazino-7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quinoxaline-
-2-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00597##
[1596]
{4-[3-Hydrazino-7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quino-
xaline-2-ylamino]-butyl}-carbamic acid-tert-butylester, a target
compound of Preparative Example 37, was obtained by the same manner
as described in Preparative Example 20.
Step 1: Preparation of
2,3-dichloro-6-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quinoxaline
[1597] Mass (M+H.sup.+): 337.1
[1598] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.93 (t, 2H), 3.86
(t, 2H), 4.53 (s, 2H), 6.91 (d, 1H), 7.23 (s, 1H), 7.32 (d, 1H),
7.83 (m, 2H).
Step 2: Preparation of
{4-[3-chloro-7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quinoxaline-2--
ylamino]-butyl}-carbamic acid-tert-butylester
[1599] Mass (M+H.sup.+): 488.2
[1600] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.33 (s, 9H), 1.41
(m, 2H), 1.56 (m, 2H), 2.91 (m, 4H), 3.40 (q, 2H), 3.72 (t, 2H),
4.41 (s, 2H), 6.78 (t, 1H), 6.89 (d, 1H), 6.93 (d, 1H), 7.18 (t,
1H), 7.25 (dd, 1H), 7.31 (d, 1H), 7.51 (d, 1H).
Step 3: Preparation of
{4-[3-hydrazino-7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quinoxaline-
-2-ylamino]-butyl}-carbamic acid-tert-butylester
[1601] Mass (M+H.sup.+): 484.1
<Example 526> Preparation of
{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino]-butyl}-carbamic
acid-tert-butylester
##STR00598##
[1603] 0.6 g of a target compound was obtained (77% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
{4-[3-hydrazino-7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-quinoxaline-
-2-ylamino]-butyl}-carbamic acid-tert-butylester (0.74 g, 1.53
mmol) prepared in step 3 of Preparative Example 37 was used.
[1604] Mass (M+H.sup.+): 508.1
[1605] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43
(m, 2H), 1.60 (m, 2H), 2.90 (q, 2H), 2.92 (m, 2H), 2.94 (s, 3H),
3.49 (q, 2H), 3.65 (q, 2H), 4.34 (s, 2H), 6.78 (t, 1H), 6.93 (d,
1H), 6.99 (d, 1H), 7.07 (s, 1H), 7.29 (s, 1H), 7.88 (d, 1H), 7.96
(t, 1H).
<Example 527> Preparation of
N.sup.1-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic
acid
##STR00599##
[1607] 0.35 g of a target compound was obtained (88% yield) by the
same manner as described in Example 58, except that
{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triazol-
o[4,3-a]quinoxaline-4-ylamino]-butyl}-carbamic acid-tert-butylester
(0.32 g, 0.63 mmol) prepared in Example 526 was used.
[1608] Mass (M+H.sup.+): 408.1
[1609] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.61 (m, 2H), 1.69
(m, 2H), 2.82 (m, 2H), 2.91 (q, 2H), 2.95 (s, 3H), 3.54 (q, 2H),
3.66 (q, 2H), 4.35 (s, 2H), 6.93 (d, 1H), 7.05 (dd, 1H), 7.10 (d,
1H), 7.31 (d, 1H), 7.65 (br, 3H), 7.91 (d, 1H).
<Example 528> Preparation of
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-3-methyl-butyramide
##STR00600##
[1611] 105 mg of a target compound was obtained (88% yield) by the
same manner as described in Example 37, except that
N.sup.1-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]tr-
iazolo[4,3-a]quinoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic
acid (150 mg, 0.24 mmol) prepared in Example 527 was used.
[1612] Mass (M+H.sup.+): 492.1
[1613] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.45 (m,
2H), 1.63 (m, 2H), 1.87 (m, 2H), 1.90 (m, 1H), 2.90 (q, 2H), 2.94
(s, 3H), 3.04 (q, 2H), 3.50 (q, 2H), 3.66 (q, 2H), 4.34 (s, 2H),
6.93 (t, 1H), 7.02 (d, 1H), 7.07 (s, 1H), 7.30 (d, 1H), 7.71 (t,
1H), 7.89 (d, 1H), 7.96 (t, 1H)
<Example 529> Preparation of
N-{4-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,2,4]triaz-
olo[4,3-a]quinoxaline-4-ylamino]-butyl}-2-(S)-fluoro-3-methyl-butyramide
##STR00601##
[1615]
N.sup.1-[7-(6,7-dihydro-4H-thiano[3,2-c]pyridine-5-yl)-1-methyl-[1,-
2,4]triazolo[4,3-a]quinoxaline-4-yl]-butane-1,4-diamine
ditrifluoroacetic acid (150 mg, 0.24 mmol) prepared in Example 527
was dissolved in 5 ml of dichloromethane, to which DCC (97 mg, 0.47
ml), DMAP (12 mg, 0.47 mmol) and 2-(S)-fluoroisovaleric acid (57
mg, 0.47 mmol) were added, followed by stirring at
0.about.5.degree. C. for 5 hours. Upon completion of the reaction,
the reaction mixture was concentrated under reduced pressure,
followed by column chromatography for separation and purification.
As a result, 40 mg of a target compound was obtained (33%
yield).
[1616] Mass (M+H.sup.+): 510.2
[1617] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 3H), 0.89
(d, 3H), 1.50 (m, 2H), 1.62 (m, 2H), 2.10 (m, 1H), 2.90 (q, 2H),
2.94 (s, 3H), 3.13 (m, 2H), 3.49 (q, 2H), 3.66 (q, 2H), 4.34 (s,
2H), 4.60 (d, 1H), 6.92 (t, 1H), 7.01 (d, 1H), 7.07 (s, 1H), 7.31
(d, 1H), 7.88 (d, 1H), 7.98 (t, 1H), 8.09 (t, 1H).
<Preparative Example 38> Preparation of
methyl-2-({4-[(tert-butoxycarbonyl)amino]-butyl}-amino)-3-hydrazinylquino-
xaline-6-carboxylate
##STR00602##
[1618] Step 1: Preparation of
methyl-2-{4-[(tert-butoxycarbonylamino)-butyl]-amino}-3-chloroquinoxaline-
-6-carboxylate
[1619] 2,3-Dichloro-quinoxaline-6-carboxylic acid methylester (2 g,
7.78 mmol) and tert-butyl(4-aminobutyl)carbamate (1.61 g, 8.56
mmol) were stirred at room temperature for 17 hours. Upon
completion of the reaction, the reaction mixture was distilled
under reduced pressure, followed by purification by MPLC
(dichloromethane/ethylacetate). As a result, a target compound was
obtained (79% yield).
[1620] Mass (M+H.sup.+): 409.2
[1621] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.40-1.58 (m, 2H), 1.56-1.65 (m, 2H), 2.93-3.00 (m, 2H), 3.46-3.52
(m, 2H), 3.89 (s, 3H), 6.78 (t, J=5.37 Hz, 1H), 7.67 (d, J=8.70 Hz,
1H), 7.92 (t, J=5.70 Hz, 1H), 8.06 (dd, J=8.76 Hz, 2.04 Hz, 1H),
8.25 (d, J=1.92 Hz, 1H).
Step 2: Preparation of
methyl-2-{4-[(tert-butoxycarbonylamino)-butyl]-amino}-3-hydrazinylquinoxa-
line-6-carboxylate
[1622]
Methyl-2-{4-[(tert-butoxycarbonylamino)-butyl]-amino}-3-chloroquino-
xaline-6-carboxylate (3.11 g, 7.61 mmol) prepared in step 1 of
Preparative Example 31, hydrazine hydrate (1.52 g, 30.4 mmol) and
diisopropylethylamine (DIPEA, 3.98 ml, 22.8 mmol) were dissolved in
isopropyl alcohol at room temperature, followed by stirring at
40.degree. C. for 18 hours. Upon completion of the reaction, the
reaction mixture was distilled under reduced pressure, which was
proceeded to the next reaction.
[1623] Mass (M+H.sup.+): 405.2
<Example 530> Preparation of
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-carboxylic acid methylester
##STR00603##
[1625] A target compound was obtained (74% yield) by the same
manner as described in step 2 of Preparative Example 20, except
that
methyl-2-{4-[(tert-butoxycarbonylamino)-butyl]-amino}-3-hydrazinylquinoxa-
line-6-carboxylate prepared in step 2 of Preparative Example 38 was
used.
[1626] Mass (M+H.sup.+): 429.2
[1627] .sup.1H NMR (300 MHz, CDCl.sub.3): .delta.1.35 (s, 9H),
1.54-1.58 (m, 2H), 1.66-1.76 (m, 2H), 3.06 (s, 3H), 3.09-3.15 (m,
2H), 3.61-3.78 (m, 2H), 3.84 (s, 3H), 4.62 (brs, 1H), 6.42 (brs,
1H), 6.93 (d, J=8.76 Hz, 2H), 7.65 (dd, J=8.52 Hz, 1.74 Hz, 1H),
7.80 (d, J=8.79 Hz, 2H), 7.99 (d, J=8.61 Hz, 1H), 8.03 (d, J=1.74
Hz, 1H).
<Example 531> Preparation of
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[4,3-a]-
quinoxaline-8-carboxylic acid
##STR00604##
[1629]
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-8-carboxylic acid methylester (2 g, 4.67 mmol)
prepared in Example 530 was dissolved in tetrahydrofuran, to which
sodium hydroxide (0.56 g, 14 mmol) dissolved in water was added at
room temperature, followed by stirring at the same temperature for
18 hours. Upon completion of the reaction, the solvent was
eliminated by distillation under reduced pressure. The pH was
adjusted to 1 with 1 N aqueous hydrochloric acid solution to form a
solid. The resulting solid was filtered and dried under reduced
pressure. As a result, a target compound was obtained (98%
yield).
[1630] Mass (M+H.sup.+): 414.7
[1631] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.42-1.51 (m, 2H), 1.62-1.70 (m, 2H), 2.93-3.00 (m, 2H), 3.05 (s,
3H), 3.54-3.60 (m, 2H), 6.79 (t, J=5.28 Hz, 1H), 7.64 (d, J=8.46
Hz, 1H), 7.96 (dd, J=8.46 Hz, 1.59 Hz, 1H), 8.57 (d, J=1.56 Hz,
1H), 8.60 (brs, 1H), 13.1 (brs, 1H).
<Example 532> Preparation of
[4-(8-isopropylcarbamoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-carbamic acid-tert-butylester
##STR00605##
[1633]
4-(4-tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-8-carboxylic acid (0.30 g, 0.72 mmol) prepared in
Example 531, isopropylamine (0.05 g, 0.86 mmol), HCTU (0.36 g, 0.86
mmol) and DIPEA (0.19 ml, 1.08 mmol) were dissolved in
dimethylformamide, followed by stirring at room temperature for 3
hours. Upon completion of the reaction, the reaction mixture was
extracted with sodium bicarbonate aqueous solution and
ethylacetate. The organic layer was washed with brine and 1 N
aqueous hydrochloric acid solution. The reactant was dried over
magnesium sulfate, filtered, and purified by MPLC (isopropyl
alcohol/dichloromethane). As a result, a target compound was
obtained (79% yield).
[1634] Mass (M+H.sup.+): 456.2
[1635] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.20 (d, J=6.63 Hz,
6H), 1.36 (s, 9H), 1.42-1.51 (m, 2H), 1.61-1.70 (m, 2H), 2.93-3.01
(m, 2H), 3.09 (s, 3H), 3.52-3.59 (m, 2H), 4.08-4.20 (m, 1H), 6.80
(t, J=5.31 Hz, 1H), 7.62 (d, J=8.49 Hz, 1H), 7.94 (dd, J=8.55 Hz,
1.65 Hz, 1H), 8.34 (t, J=6.81 Hz, 1H), 8.41 (t, J=5.73 Hz, 1H),
8.46 (d, J=1.50 Hz, 1H).
[1636] The compound prepared in Example 532 was obtained in the
form of the primary amine by removal of the protecting group by
trifluoroacetic acid. The compound was obtained in quantitative
yield and can be used in the next reaction to produce various amide
compounds.
[1637] Examples of the compounds prepared by the same manner as
described in Examples 530.about.532 are shown in Table 37
below.
TABLE-US-00037 TABLE 37 Ex- ample Structure Name Data Ex- ample 533
##STR00606## [4-(8- carbamoyl- 1-methyl- [1,2,4]tri- azolo[4,3-
a]quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- butylester
Mass (M + H.sup.+): 414.2; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.36 (s, 9H), 1.44-1.49 (m, 2H), 1.63-1.68 (m, 2H),
2.93-3.00 (m, 2H), 3.08 (s, 3H), 3.55-3.57 (m, 2H), 6.80 (brs, 1H),
7.46 (s, 1H), 7.61 (d, J = 8.46 Hz, 1H), 7.94 (d, J = 7.23 Hz, 1H),
8.41 (t, J = 8.85 Hz, 1 H), 8.12 (s, 1H), 8.48 (s, 1H). Ex- ample
534 ##STR00607## 4-(4- isobutylamino- butylamino)- 1-methyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 8-carboxylic acid
isopropylamide Mass (M + H.sup.+): 426.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.97 (d, J = 6.85 Hz, 6H), 1.21 (d, J = 6.55 Hz,
6H), 1.60-1.71 (m, 2H), 2.29-2.38 (m, 1H), 3.06-3.10 (m, 5H),
3.55-3.63 (m, 2H), 4.11-4.18 (m, 1H), 7.62 (d, J = 8.45 Hz, 1H),
7.70 (t, J = 5.40 Hz, 1H), 7.95 (dd, J = 8.55 Hz, 1.65 Hz, 1H),
8.36 (d, J = 7.65 Hz, 1H), 8.43 (t, J = 5.70 Hz, 1H), 8.48 (d, J =
1.60 Hz, 1H, 1.46-1.52 (m, 2H). Ex- ample 535 ##STR00608## 4-(4-
benzylamino- butylamino)- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 8-carboxylic acid isopropylamide Mass (M + H.sup.+):
460.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.21 (d, J = 6.60 Hz,
6H), 1.60-1.67 (m, 2H), 1.72-1.78 (m, 2H), 3.07 (s, 3H), 3.31- 3.35
(m, 2H), 3.59- 3.62 (m, 2H), 4.11- 4.19 (m, 1H), 7.44 (t, J = 7.25
Hz, 2H), 7.51 (t, J = 7.35 Hz, 1H), 7.61 (d, J = 8.45 Hz, 1H),
7.82-7.84 (m, 2H), 7.94 (dd, J = 8.55 Hz, 1.55 Hz, 1H), 8.36 (d, J
= Hz, 1H), 8.43-8.47 (m, 3H). Ex- ample 536 ##STR00609## {4-[8-(2-
dimethylamino- ethylcar- bamoyl)- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- carbamic Mass (M + H.sup.+):
485.3; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.42-1.52 (m, 2H), 1.62-1.69 (m, 2H), 2.20 (s, 6H), 2.42-2.46 (m,
2H), 2.94-3.00 (m, 2H), 3.09 (s, 3H), 3.37- 3.43 (m, 2H), 3.53-
acid-tert- 3.59 (m, 2H), 6.79 butylester (t, J = 4.89 Hz, 1H), 7.62
(d, J = 8.49 Hz, 1H), 7.90 (dd, J = 8.55 Hz, 1.47 Hz, 1H), 8.40 (t,
J = 5.64 Hz, 1H), 8.45 (d, J = 1.23 Hz, 1H), 8.53 (t, J = 5.58 Hz,
1H). Ex- ample 537 ##STR00610## 4-(4- benzoylamino)- 1-methyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 8-carboxylic acid-(2-
dimethylamino- ethyl)-amide Mass (M + H.sup.+): 488.9 Ex- ample 538
##STR00611## [4-(1- methyl-8- phenylcar- bamoyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4-ylamino)- butyl]- carbamic Mass (M +
H.sup.+): 490.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s,
9H), 1.45-1.52 (m, 2H), 1.63-1.70 (m, 2H), 2.94-3.00 (m, 2H), 3.12
(s, 3H), 3.55-3.61 (m, 2H), 6.78-6.82 (m, 1H), acid-tert- 7.12 (t,
J = 7.38 butylester Hz, 1H), 7.38 (t, J = 8.04 Hz, 2H), 7.70 (d, J
= 8.49 Hz, 1H), 7.80 (d, J = 7.77 Hz, 2H), 8.12 (dd, J = 8.55 Hz,
1.62 Hz, 1H), 8.49 (t, J = 5.67 Hz, 1H), 8.57(d, J = 1.53 Hz, 1H),
10.40 (s, 1H). Ex- ample 539 ##STR00612## N-{4-[8- (4-benzyl-
piperazine- 1-carbonyl)- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- Mass (M + H.sup.+): 576.5;
.sup.1H NMR (300 MHz, DMSO-d6): .delta.1.60- 1.64 (m, 2H), 1.66-
1.72 (m, 2H), 3.05 (s, 3H), 3.14-3.18 (m, 3H), 3.20-3.35 (m, 4H),
3.55-3.65 (m, 6H), 4.34 (brs, benzamide 2H), 7.40-7.44 (m, 6H),
7.46-7.55 (m, 2H), 7.66-7.74 (m, 3H), 7.82-7.85 (m, 2H), 8.07 (d, J
= 1.23 Hz, 1H), 8.53- 8.56 (m, 1H). Ex- ample 540 ##STR00613##
N-{4-[1- methyl-8- (piperazine- 1-carbonyl)- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4-ylamino]- butyl}- benzamide Mass (M + H.sup.+):
486.5
<Preparative Example 39> Preparation of
tert-butyl-[4-(3-hydrazinyl-6-nitroquinoxaline-2-ylamino)-butyl]-carbamat-
e
##STR00614##
[1638] Step 1: Preparation of 2,3-dichloro-6-nitroquinoxaline
[1639] 6-Nitroquinoxaline-2,3-(1H,4H)-dione (12 g, 59.0 mmol),
thionylchloride (28.1 g, 236 mmol), and catalytic amount of
dimethylformamide (0.86 g, 11.8 mmol) were reflux stirred in
dichloroethane for 2 hours. Upon completion of the reaction, the
solvent was eliminated and the temperature was lowered to
0-5.degree. C. to form a solid. The resulting solid was filtered
and dried under reduced pressure. As a result, 12.3 g of a target
compound was obtained (87% yield).
[1640] Mass (M+H.sup.+): 244.1
[1641] .sup.1H NMR (300 MHz, DMSO-d6) .delta.8.31 (d, J=9.15 Hz,
1H), 8.60 (d, J=9.15 Hz, 1H), 8.88 (s, 1H).
Step 2: Preparation of
tert-butyl-[4-(3-chloro-6-nitroquinoxaline-2-ylamino)-butyl]-carbamate
[1642] 2.2 g of a target compound was obtained (92% yield) by the
same manner as described in step 1 of Preparative Example 20,
except that 2,3-dichloro-6-nitroquinoxaline (2.55 g, 10.5 mmol)
prepared in step 1 of Preparative Example 39 was used.
[1643] Mass (M+H.sup.+): 396.2
[1644] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.43-1.49 (m, 2H), 1.63-1.67 (m, 2H), 2.95-3.00 (m, 2H), 3.50-3.54
(m, 2H), 6.79 (t, J=5.20 Hz, 1H), 7.73 (d, J=9.20 Hz, 1H), 8.24 (t,
J=5.70 Hz, 1H), 8.33 (dd, J=9.25 Hz, 2.65 Hz, 1H), 58.55 (d, J=2.60
Hz, 1H)
Step 3: Preparation of
tert-butyl-[4-(3-hydrazinyl-6-nitroquinoxaline-2-ylamino)-butyl]-carbamat-
e
[1645] A target compound was obtained (quantitative yield) by the
same manner as described in step 2 of Preparative Example 39,
except that
tert-butyl-[4-(3-chloro-6-nitroquinoxaline-2-ylamino)-butyl]-carbamate
(2.30 g, 5.81 mmol) prepared in step 2 of Preparative Example 39
was used. The following reaction was carried out without
purification.
[1646] Mass (M+H.sup.+): 392.2
<Example 541> Preparation of
[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester
##STR00615##
[1648] A target compound was obtained (76% yield) by the same
manner as described in step 3 of Preparative Example 5, except that
tert-butyl-[4-(3-hydrazinyl-6-nitroquinoxaline-2-ylamino)-butyl]-carbamat-
e prepared in step 3 of Preparative Example 39 was used.
[1649] Mass (M+H.sup.+): 416.2
[1650] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.37 (s, 9H),
1.44-1.50 (m, 2H), 1.64-1.70 (m, 2H), 2.95-3.00 (m, 2H), 3.09 (s,
3H), 3.58-3.62 (m, 2H), 6.81 (t, J=5.10 Hz, 1H), 7.70 (d, J=8.95
Hz, 1H), 8.27 (dd, J=8.85 Hz, 1.70 Hz, 1H), 8.78 (d, J=1.35 Hz,
1H), .delta.9.00 (t, J=5.65 Hz, 1H)
<Example 542> Preparation of
[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester
##STR00616##
[1652]
[4-(1-Methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-b-
utyl]-carbamic acid-tert-butylester (1.50 g, 3.61 mmol) prepared in
Example 541 and Pd/C (10 W %) were loaded in ethanol, followed by
stirring at room temperature at 5 bar of hydrogen for 4 hours. Upon
completion of the reaction, paladium catalyst was filtered and
eliminated. The filtrate was distilled under reduced pressure,
followed by recrystallization in methanol. As a result, a target
compound was obtained (92% yield).
[1653] Mass (M+H.sup.+): 386.3
[1654] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.37 (s, 9H),
1.43-1.49 (m, 2H), 1.60-1.66 (m, 2H), 2.94-2.97 (m, 2H), 2.99 (s,
3H), 3.46-3.50 (m, 2H), 5.83 (brs, 2H), 6.78 (dd, J=8.70 Hz, 2.20
Hz, 1H), 6.81 (t, J=5.60 Hz, 1H), 7.38 (d, J=8.90 Hz, 1H), 7.40 (d,
J=2.10 Hz, 1H), 7.66 (brs, 1H).
<Example 543> Preparation of
[4-(8-isobutylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester
##STR00617##
[1656] A target compound was obtained (69% yield) by the same
manner as described in Example 70, except that
[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]--
carbamic acid-tert-butylester (0.50 g, 1.30 mmol) prepared in
Example 542 was used.
[1657] Mass (M+H.sup.+): 455.5
[1658] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.15 (d, J=6.80 Hz,
6H), 1.37 (s, 9H), 1.44-1.49 (m, 2H), 1.62-1.69 (m, 2H), 2.61-2.66
(m, 1H), 2.95-3.00 (m, 2H), 3.02 (s, 3H), 3.49-3.53 (m, 2H), 6.81
(t, J=5.40 Hz, 1H), 7.53 (d, J=8.80 Hz, 1H), 7.58 (dd, J=8.80 Hz,
2.00 Hz, 1H), 7.95 (t, J=5.75 Hz, 1H), 8.80 (d, J=1.85 Hz, 1H),
10.1 (s, 1H).
<Example 544> Preparation of
N-[4-(4-aminobutylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-yl]-
-isobutyramide ditrifluoroacetic acid
##STR00618##
[1660] A target compound was obtained by the same manner as
described in Example 58, except that
[4-(8-isobutylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-
-butyl]-carbamic acid-tert-butylester (0.15 g, 0.33 mmol) prepared
in Example 543 was used.
[1661] Mass (M+H.sup.+): 356.3
<Example 545> Preparation of
N-[4-(8-isobutylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-2,2-dimethyl-propionamide
##STR00619##
[1663] A target compound was obtained (64% yield) by the same
manner as described in Example 59, except that
N-[4-(4-aminobutylamino)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-8-yl]-
-isobutyramide ditrifluoroacetic acid prepared in Example 544 was
used.
[1664] Mass (M+H.sup.+): 439.4
[1665] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.07 (s, 9H), 1.15
(d, J=6.80 Hz, 6H), 1.46-1.52 (m, 2H), 1.62-1.67 (m, 2H), 2.61-2.66
(m, 1H), 3.02 (s, 3H), 3.07-3.12 (m, 2H), 3.50-3.54 (m, 2H), 7.43
(t, J=5.65 Hz, 1H), 7.52 (d, J=8.75 Hz, 1H), 7.58 (dd, J=8.90 Hz,
2.10 Hz, 1H), 7.95 (t, J=5.75 Hz, 1H), 8.80 (s, 1H), 10.1 (s,
1H).
[1666] Examples of the compounds prepared by the same manner as
described in Examples 543 and 544 are shown in Table 38 below.
TABLE-US-00038 TABLE 38 Example Structure Name Data Example 546
##STR00620## [4-(8- acetamino- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- Mass (M +
H.sup.+): 427.6; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.37 (s,
9H), 1.45-1.49 (m, 2H), 1.62-1.66 (m, 2H), 2.10 (s, 3H), 2.95-2.99
(m, 2H), 3.00 (s, 3H), 3.49-3.53 (m, 2H), 6.80 (t, J = 5.35
butylester Hz, 1H), 7.52-7.57 (m, 2H), 7.95 (t, J = 5.70 Hz, 1H),
8.69 (d, J = 1.70 Hz, 1H), 10.2 (s, 1H). Example 547 ##STR00621##
N-[4-(8- acetamino- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino)- butyl]-2,2- dimethyl- propionamide Mass (M + H.sup.+):
411.6; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.07 (s, 9H),
1.46-1.52 (m, 2H), 1.61-1.67 (m, 2H), 2.10 (s, 3H), 3.00 (s, 3H),
3.06-3.10 (m, 2H), 3.50-3.54 (m, 2H), 7.43 (t, J = 5.65 Hz, 1H),
7.52-7.53 (m, 1H), 7.55-7.57 (m, 1H), 7.95 (t, J = 5.55 Hz, 1H),
8.69 (d, J = 1.95 Hz, 1H), 10.2 (s, 1H). Example 548 ##STR00622##
N-[4-(8- acetamino- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino)- butyl]- benzamide Mass (M + H.sup.+): 431.9; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.60- 1.65 (m, 2H), 1.70-1.76 (m,
2H), 2.10 (s, 3H), 3.00 (s, 3H), 3.30-3.34 (m, 2H), 3.54-3.58 (m,
2H), 7.44 (t, J = 7.20 Hz, 2H), 7.49-7.56 (m, 3H), 7.82-7.83 (m,
2H), 7.98 (t, J = 5.80 Hz, 1H), 8.46 (t, J = 5.50 Hz, 1H), 8.69 (d,
J = 1.90 Hz, 1H), 10.2 (s, 1H). Example 549 ##STR00623## N-[4-(8-
isobutylamino- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline
4-ylamino)- butyl]- benzamide Mass (M + H.sup.+): 459.5; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.15 (d, J = 6.85 Hz, 6H), 1.61-1.67
(m, 2H), 1.70-1.76 (m, 2H), 2.61-2.65 (m, 1H), 3.01 (s, 3H),
3.30-3.36 (m, 2H), 3.54-3.59 (m, 2H), 7.44 (t, J = 7.35 Hz, 2H),
7.49-7.53 (m, 2H), 7.57 (dd, J = 8.70 Hz, 1.75 Hz, 1H), 7.83 (d, J
= 7.65 Hz, 2H), 7.98 (t, J = 5.70 Hz, 1H), 8.46 (t, J = 5.40 Hz,
1H), 8.80 (s, 1H), 10.1 (s, 1H).
<Preparative Example 40> Preparation of
N-[4-(3-hydrazino-6-nitroquinoxaline-2-ylamino)butyl]-3-methyl-butyramide
##STR00624##
[1667] Step 1: Preparation of
N-[4-(3-chloro-6-nitroquinoxaline-2-ylamino)-butyl]-3-methyl-butyramide
[1668] 1.5 g of a target compound was obtained (96% yield) by the
same manner as described in step 1 of Preparative Example 20,
except that 2,3-dichloro-6-nitroquinoxaline (1 g, 4.1 mmol) and
N-(4-aminobutyl)-3-methyl-butyramide ditrifluoroacetic acid (2.46
g, 6.15 mmol) prepared in step 1 of Preparative Example 18 were
used.
[1669] Mass (M+H.sup.+): 378.2
[1670] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.24 (d, 6H), 1.31 (m,
3H), 1.40 (m, 2H), 1.52 (m, 2H), 2.73 (q, 2H), 3.56 (q, 2H), 6.67
(s, 1H), 6.72 (t, 1H), 8.20 (t, 1H), 8.28 (d, 1H), 8.50 (d,
1H).
Step 2: Preparation of
N-[4-(3-hydrazino-6-nitroquinoxaline-2-ylamino)
butyl]-3-methyl-butyramide
[1671] 2.45 g of a target compound was obtained (67% yield) by the
same manner as described in step 2 of Preparative Example 20,
except that
N-[4-(3-chloro-6-nitroquinoxaline-2-ylamino)-butyl]-3-methyl-butyramide
(3.7 g, 9.74 mmol) prepared in step 1 of Preparative Example 40 was
used. The following reaction was carried out without
purification.
[1672] Mass (M+H.sup.+): 376.2
[1673] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H) 1.40 (m,
2H), 1.55 (m, 2H), 1.86 (d, 2H), 1.89 (m, 1H), 3.00 (q, 2H), 3.38
(br, 3H), 3.42 (q, 2H), 7.25 (d, 1H), 7.55 (t, 1H), 7.71 (s, 1H),
7.72 (d, 1H), 7.98 (t, 1H).
<Example 550> Preparation of
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide
##STR00625##
[1675] 1.8 g of a target compound was obtained (70% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that N-[4-(3-hydrazino-6-nitroquinoxaline-2-ylamino)
butyl]-3-methyl-butyramide (2.4 g, 6.4 mmol) prepared in step 2 of
Preparative Example 40 was used.
[1676] Mass (M+H.sup.+): 400.2
[1677] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.45 (m,
2H), 1.64 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 3.04 (q, 2H), 3.05
(s, 3H), 3.57 (q, 2H), 7.64 (d, 1H), 7.70 (t, 1H), 8.23 (d, 1H),
8.74 (s, 1H), 8.95 (t, 1H)
<Example 551> Preparation of
N-[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide
##STR00626##
[1679] 0.72 g of a target compound was obtained (75% yield) by the
same manner as described in Example 243, except that
3-methyl-N-[4-(1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-butyramide (1 g, 2.50 mmol) prepared in Example 549 was
used.
[1680] Mass (M+H.sup.+): 370.0
[1681] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.43 (m,
2H), 1.59 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 2.94 (s, 3H), 3.04
(q, 2H), 3.43 (q, 2H), 5.32 (s, 2H), 6.70 (t, 1H), 7.29 (m, 2H),
7.35 (t, 1H), 7.70 (t, 1H).
[1682] The compounds prepared by using
N-[4-(8-amino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-3-methyl-butyramide prepared in Example 550 are shown in Table 39
below.
TABLE-US-00039 TABLE 39 Example Structure Name Data Example 552
##STR00627## 3-methyl-N- [4-(1- methyl-8- propylamino-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- butyramide
Mass (M + H.sup.+): 412.0; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.80 (d, 6H), 0.98 (m, 3H), 1.14 (m, 2H), 1.40 (m, 2H), 1.58
(m, 4H), 1.88 (t, 3H), 2.97 (s, 3H), 3.05 (q, 2H), 3.40 (q, 2H),
5.87 (t, 1H), 6.72 (d, 1H), 7.19 (s, 1H), 7.32 (d, 1H), 7.68 (t,
1H), 8.84 (br, 1H). Example 553 ##STR00628## N-{4-[8-(3- cyano-
propylamino)- 1-methyl- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino]- butyl}-3- methyl- Mass (M + H.sup.+): 437.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.43 (m, 2H), 1.70 (m,
2H), 1.82 (m, 4H), 1.87 (m, 4H), 2.46 (m, 2H), 3.02 (m, butyramide
4H), 3.41 (m, 5H), 5.71 (s, 1H), 6.93 (d, 1H), 7.20 (s, 1H), 7.43
(d, 1H), 7.55 (t, 1H), 7.69 (t, 1H). Example 554 ##STR00629##
N-{4-[8-(3- ethyl- thioureido)- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino]- butyl}-3- methyl- Mass (M + H.sup.+):
471.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.86 (d, 6H), 1.23
(t, 3H), 1.45 (m, 2H) , 1.63 (m, 2H), 1.71 (m, 1H), 1.87 (d, 2H),
2.98 (s, butyramide 3H), 3.04 (q, 2H), 3.48 (q, 2H), 3.75 (t, 3H),
7.47 (d, 1H), 7.49 (t, 1H), 7.62 (d, 1H), 7.69 (m, 2H), 7.95 (t,
1H).
<Example 555> Preparation of
N-[4-(7-methoxy-1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide
##STR00630##
[1684]
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamin-
o)-butyl]-3-methyl-butyramide (100 mg, 0.26 mmol) prepared in
Example 285 was dissolved in 2 ml of 60% nitric acid aqueous
solution, to which 1 ml of sulfuric acid was added, followed by
reaction at room temperature for 3 hours. Upon completion of the
reaction, the reaction mixture was extracted with ethylacetate and
water. The organic layer was dried over magnesium sulfate, followed
by distillation under reduced pressure. The resulting solid was
recrystallized in ethanol, and as a result 25 mg of a target
compound was obtained (22% yield).
[1685] Mass (M+H.sup.+): 430.1
[1686] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.46
(m, 2H), 1.62 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 2.98 (s, 3H),
3.01 (q, 2H), 3.56 (q, 2H), 3.98 (s, 3H), 7.27 (s, 1H), 7.70 (t,
1H), 8.52 (s, 1H), 8.85 (t, 1H)
<Example 556> Preparation of
N-[4-(8-amino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide
##STR00631##
[1688] 0.56 g of a target compound was obtained (67% yield) by the
same manner as described in Example 243, except that
N-[4-(7-methoxy-1-methyl-8-nitro-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide (0.9 g, 2.10 mmol) prepared in
Example 555 was used.
[1689] Mass (M+H.sup.+): 400.2
[1690] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.48
(m, 2H), 1.65 (m, 2H), 1.89 (d, 2H), 1.92 (m, 1H), 2.95 (s, 3H),
3.13 (q, 2H), 3.55 (q, 2H), 3.89 (s, 3H), 7.26 (s, 1H), 7.70 (s,
1H), 7.76 (t, 1H), 9.40 (br, 2H).
[1691] The compounds prepared by using
N-[4-(8-amino-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylam-
ino)-butyl]-3-methyl-butyramide prepared in Example 556 are shown
in Table 40 below.
TABLE-US-00040 TABLE 40 Example Structure Name Data Example 557
##STR00632## N-[4-(7- methoxy-1- methyl-8- methylamino-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl-
Mass (M + H.sup.+): 414.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.79 (d, 6H), 1.20 (d, 3H), 1.45 (m, 2H), 1.61 (m, 2H), 1.87
(d, 2H), 1.90 (m, 1H), 2.80 butyramide (q, 2H), 3.02 (q, 2H), 3.05
(s, 3H), 3.40 (q, 1H), 3.85 (s, 3H), 6.98 (s, 1H), 7.03 (s, 1H),
7.44 (t, 1H), 7.70 (t, 1H). Example 558 ##STR00633## N-[4-(8-
hydroxyamino- 7-methoxy- 1-methyl- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M - H.sup.+):
414.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81 (d, 6H), 1.20
(br, 1H), 1.46 (m, 2H), 1.65 (m, 2H), 1.89 (m, 1H), 2.86 (s, 3H),
3.05 butyramide (s, 2H), 3.30 (d, 1H), 3.60 (q, 2H), 4.23 (s, 3H),
6.80 (s, 1H), 7.39 (s, 1H), 7.71 (t, 1H), 9.22 (t, 1H). Example 559
##STR00634## N-[4-(7- methoxy-1- methyl-8- propylamino-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl-
Mass (M + H.sup.+): 442.3; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.80 (d, 6H), 0.94 (t, 3H), 1.43 (m, 2H), 1.61 (m, 4H), 1.86
(d, 2H), 1.87 (m, 1H), 3.00 butyramide (s, 3H), 3.04 (q, 2H), 3.11
(s, 2H), 3.45 (m, 2H), 3.86 (s, 3H), 5.09 (t, 1H), 6.98 (s, 1H),
7.06 (s, 1H), 7.45 (t, 1H), 7.70 (t, 1H). Example 560 ##STR00635##
N-[4-(7- methoxy-1- methyl-8- prop-2- ylamino- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]-3- Mass (M + H.sup.+):
438.3; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.44
(m, 2H), 1.62 (m, 2H), 1.86 (d, 2H), 1.90 (m, 1H), 3.05 (s, 3H),
3.09 methyl- (q, 2H), 3.46 butyramide (q, 2H), 3.86 (s, 3H), 4.03
(d, 2H), 5.67 (t, 1H), 7.02 (s, 1H), 7.31 (s, 1H), 7.53 (t, 1H),
7.71 (t, 2H). Example 561 ##STR00636## N-{4-[8-(3- isopropyl-
ureido)-7- methoxy-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino]- butyl}-3- methyl- Mass (M + H.sup.+): 485.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.45 (m, 2H), 1.62 (m,
2H), 1.87 (d, 2H), 2.01 (m, 1H), 2.93 (s, 3H), 3.04 (q, 2H), 3.49
butyramide (q, 2H), 3.80 (m, 1H), 3.91 (s, 3H), 6.86 (t, 1H), 7.09
(s, 1H), 7.70 (d, 1H), 7.78 (t, 1H), 8.02 (s, 1H), 9.12 (s, 1H).
Example 562 ##STR00637## N-{4-[7- methoxy-1- methyl-8-(3- methyl-
butyrylamino)- [1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino]-
butyl}-3- Mass (M + H.sup.+): 484.3; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.81 (d, 6H), 0.92 (d, 6H), 1.46 (m, 2H), 1.64 (m,
2H), 1.87 (d, 2H), 2.06 (m, 1H), 2.15 methyl- (m, 1H), 2.25
butyramide (d, 2H), 2.94 (s, 3H), 3.10 (q, 2H), 3.67 (q, 2H), 3.94
(s, 3H), 7.34 (t, 1H), 7.74 (t, 1H), 9.07 (s, 1H), 9.27 (s, 1H),
9.50 (t, 1H). Example 563 - ##STR00638## N-{7- methoxy-1-
methyl-4-[4- (3-methyl- butyrylamino)- [1,2,4]triazolo [4,3-a]
quinoxaline- 8-ylamino]- butyl}-3,3- Mass (M + H.sup.+): 498.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.78 (d, 6H), 1.01 (d, 9H),
1.45 (m, 2H), 1.63 (m, 2H), 1.86 (d, 2H), 1.88 (m, 1H), 2.31
dimethyl- (s, 2H), 2.92 butyramide (s, 3H), 3.05 (q, 2H), 3.48 (q,
2H), 3.89 (s, 3H), 7.12 (t, 1H), 7.69 (s, 1H), 7.95 (s, 1H), 8.98
(t, 1H), 9.09 (s, 1H). Example 564 ##STR00639## N-{4-[7- methoxy-1-
methyl-8-(3- phenyl- ureido)- [1,2,4]triazolo [4,3-a] quinoxaline
4-ylamino]- butyl}-3- Mass (M + H.sup.+): 518.3; .sup.1H NMR (500
MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.44 (m, 2H), 1.62 (m, 2H),
1.87 (d, 2H), 1.90 (m, 1H), 2.89 (s, 3H), 3.05 methyl- (q, 2H),
3.49 butyramide (q, 2H), 3.52 (s, 3H), 3.92 (s, 2H), 7.22 (m, 5H),
7.50 (t, 1H), 7.70 (s, 1H), 7.90 (d, 1H), 7.98 (t, 1H). Example 565
##STR00640## N-[4-(8- methanesulfonyl- amino-7- methoxy-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- Mass (M
- H.sup.+): 476.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.86 (d, 2H), 1.87 (m, 1H), 2.92
(s, 3H), 2.96 methyl- (s, 3H), 3.05 butyramide (q, 2H), 3.50 (q,
6H), 3.91 (s, 3H), 7.16 (s, 1H), 7.70 (t, 1H), 7.97 (s, 1H), 8.10
(t, 1H), 9.12 (s, 1H). Example 566 ##STR00641## N-[4-(8-
dimethanesulfonyl- amino- 7-methoxy-1- methyl- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl- Mass (M -
H.sup.+): 556.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.82 (d,
6H), 1.44 (m, 2H), 1.64 (m, 2H), 1.86 (d, 2H), 1.88 (m, 1H), 2.97
(s, 3H), 3.05 (q, 2H), 3.50 butyramide (s, 6H), 3.52 (q, 2H), 3.91
(s, 3H), 7.22 (s, 1H), 7.69 (t, 1H), 7.95 (s, 1H), 8.44 (t, 1H).
Example 567 ##STR00642## N-{4-[7- methoxy-1- methyl-8-(2- methyl-
propane-1- sulfonylamino- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino]- Mass (M + H.sup.+): 520.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.79 (d, 6H), 0.97 (d, 6H), 1.45 (m, 2H), 1.63 (m,
2H), 1.86 (d, 2H), 1.90 (m, 1H), 2.15 butyl}-3- (m, 1H), 2.91
methyl- (d, 2H), 2.93 butyramide (s, 3H), 3.10 (q, 2H), 3.50 (q,
2H), 3.88 (s, 3H), 7.14 (s, 1H), 7.70 (t, 1H), 7.99 (s, 1H), 8.09
(t, 1H), 9.14 (s, 1H). Example 568 ##STR00643## N-{4-[7- methoxy-1-
methyl-8-(3- phenyl- ureido)- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino]- butyl}-3- methyl- Mass (M + H.sup.+): 519.3; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.46 (m, 2H), 1.63 (m,
2H), 1.87 (d, 2H), 1.95 (m, 1H), 2.97 (s, 3H), 3.04 (q, 2H), 3.50
butyramide (q, 2H), 3.96 (s, 3H), 6.97 (dd, 1H), 7.15 (s, 1H), 7.27
(dd, 1H), 7.46 (dd, 1H), 7.70 (t, 1H), 7.87 (t, 1H), 8.45 (s, 1H),
9.14 (s, 1H), 9.37 (s, 1H). Example 569 ##STR00644## N-{4-[8-(3-
isopropyl- thioureido)- 7-methoxy-1- methyl- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino]- butyl}-3- methyl- Mass (M +
H.sup.+): 501.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.15 (d, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.86 (d, 2H), 1.90
(m, 1H), 2.95 (s, 3H), 3.05 butyramide (q, 2H), 3.50 (q, 2H), 3.91
(s, 3H), 4.38 (m, 1H), 7.13 (s, 1H), 7.70 (t, 1H), 7.97 (t, 1H),
8.23 (d, 1H), 8.97 (s, 1H), 9.26 (s, 1H)
<Example 570> Preparation of
{4-[8-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester
##STR00645##
[1693] The compound of Example 570 was prepared by the following
two-step reaction.
##STR00646##
Step 1: Preparation of
tert-butyl-{4-[(8-(methoxy(methyl)carbamoyl)-1-methyl-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-yl)amino]-butyl}-carbamate
[1694]
4-(4-Tert-butoxycarbonylamino-butylamino)-1-methyl-[1,2,4]triazolo[-
4,3-a]quinoxaline-8-carboxylic acid (0.30 g, 0.72 mmol) and
methoxylmethylamine hydrochloride (0.08 g, 0.86 mmol) prepared in
Example 531, HCTU (0.36 g, 0.86 mmol) and DIPEA (0.38 ml, 2.16
mmol) were dissolved in dimethylformamide, followed by stirring at
room temperature for 3 hours. Upon completion of the reaction, the
reaction mixture was extracted with ethylacetate and sodium
bicarbonate aqueous solution. The organic layer was washed with 1 N
aqueous hydrochloric acid solution and brine. The reactant was
purified by MPLC (isopropyl alcohol/dichloromethane), and as a
result, a target compound was obtained (86% yield).
[1695] Mass (M+H.sup.+): 458.2
[1696] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.36 (s, 9H),
1.44-1.49 (m, 2H), 1.64-1.69 (m, 2H), 2.94-3.01 (m, 2H), 3.03 (s,
3H), 3.58 (s, 3H), 3.62 (s, 3H), 6.80 (brs, 1H), 7.63 (d, J=8.40,
1H), 7.75 (d, J=8.40 Hz, 1H), 8.39 (s, 1H), 8.53 (brs, 1H).
Step 2: Preparation of
{4-[8-(4-methoxy-benzoyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl-
amino]-butyl}-carbamic acid-tert-butylester
[1697]
Tert-butyl-{4-[(8-(methoxy(methyl)carbamoyl)-1-methyl-[1,2,4]triazo-
lo[4,3-a]quinoxaline-4-yl)amino]-butyl}-carbamate (0.10 g, 0.22
mmol) prepared in step 1 above was dissolved in anhydrous
tetrahydrofuran, to which excessive 4-methoxyphenylmagnesiumbromide
was added in the presence of nitrogen, followed by reflux stirring
for 15 minutes. Upon completion of the reaction, the reaction was
terminated by adding 1 N aqueous hydrochloric acid solution at room
temperature, followed by extraction with ethylacetate. The
collected organic layer was washed with brine and dried over
magnesium sulfate. The reactant was purified by MPLC (isopropyl
alcohol/dichloromethane), and as a result, a target compound was
obtained (78% yield).
[1698] Mass (M+H.sup.+): 505.2
[1699] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.43-1.50 (m, 2H), 1.65-1.70 (m, 2H), 2.94-3.01 (m, 5H), 3.58-3.60
(m, 2H), 3.89 (s, 3H), 6.80 (brs, 1H), 7.11-7.13 (m, 2H), 7.67-7.70
(m, 1H), 7.79-7.87 (m, 3H), 8.41 (s, 1H), 8.60 (brs, 1H).
<Example 571> Preparation of
[4-(8-benzoyl-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl-
]-carbamic acid-tert-butylester
##STR00647##
[1701] A target compound was obtained by the same manner as
described in Example 570, except that phenylmagnesiumbromide was
used instead of 4-methoxyphenylmagnesiumbromide in step 2 of
Example 570.
[1702] Mass (M+H.sup.+): 475.2
[1703] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H),
1.43-1.50 (m, 2H), 1.63-1.70 (m, 2H), 2.95-3.00 (m, 5H), 3.58-3.60
(m, 2H), 6.80 (brs, 1H), 7.58-7.63 (m, 4H), 7.68-7.84 (m, 3H), 8.45
(s, 1H), 8.67 (t, J=5.10 Hz, 1H)
<Preparative Example 41> Preparation of
[4-(3-hydrazino-6-fluoro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (c) and
[4-(3-hydrazino-7-fluoro-6-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (d)
##STR00648##
[1704] Step 1: Preparation of
2,3-dichloro-7-fluoro-6-methoxy-quinoxaline
[1705] Mass (M+H.sup.+): 247.2
Step 2: Preparation of
[4-(3-chloro-6-fluoro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (a) and
[4-(3-chloro-7-fluoro-6-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (b) mixture
[1706] Mass (M+H.sup.+): 399.1
Step 3: Preparation of
[4-(3-hydrazino-6-fluoro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (c) and
[4-(3-hydrazino-7-fluoro-6-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (d) mixture
[1707] Mass (M+H.sup.+): 395.2
<Example 572> Preparation of [4-(8-fluoro-7-methoxy
1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butyl]-carbamic
acid-tert-butylester
##STR00649##
[1709] 580 mg of a target compound was obtained (39% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that
[4-(3-hydrazino-6-fluoro-7-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (c) and
[4-(3-hydrazino-7-fluoro-6-methoxy-quinoxaline-2-ylamino)-butyl]-carbamic
acid-tert-butylester (d) mixture (1.4 g, 3.55 mmol) prepared in
step 3 of Preparative Example 41 was used.
[1710] Mass (M+H.sup.+): 419.2
[1711] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.42 (m,
2H), 1.60 (m, 2H), 2.91 (m, 2H), 2.95 (s, 3H), 3.48 (q, 2H), 3.90
(s, 3H), 6.75 (t, 1H), 7.25 (d, 1H), 7.88 (d, 1H), 8.07 (t,
1H).
<Example 573> Preparation of
[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid-tert-butylester
##STR00650##
[1713] 185 mg of a target compound was obtained (12% yield) by
separating and purifying the compound produced as a structural
isomer in the course of reaction in Example 572.
[1714] Mass (M+H.sup.+): 419.2
[1715] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.32 (s, 9H), 1.42 (m,
2H), 1.59 (m, 2H), 2.91 (q, 2H), 3.05 (s, 3H), 3.45 (q, 2H), 3.95
(s, 3H), 6.74 (t, 1H), 7.38 (dd, 1H), 7.65 (s, 1H), 8.00 (t,
1H).
[1716] The compounds of Examples 574 and 575 were prepared by the
same manner as described in Examples 572 and 573, except that
N-(4-aminobutyl)-3-methyl-butyramide was used instead of
tert-butyl-(N-aminobutyl)carbonate in step 2 of Preparative Example
41.
<Example 574> Preparation of
N-[4-(8-fluoro-7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide
##STR00651##
[1718] Mass (M+H.sup.+): 403.2
[1719] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d, 6H), 1.44
(m, 2H), 1.62 (m, 2H), 1.86 (d, 2H), 1.89 (m, 1H), 2.95 (s, 3H),
3.04 (q, 2H), 3.48 (q, 2H), 3.90 (s, 3H), 7.25 (d, 1H), 7.70 (t,
1H), 7.87 (d, 1H), 8.08 (t, 1H).
<Example 575> Preparation of
N-[4-(7-fluoro-8-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide
##STR00652##
[1721] Mass (M+H.sup.+): 403.2
[1722] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44
(m, 2H), 1.60 (m, 2H), 1.86 (d, 2H), 1.90 (m, 1H), 3.03 (q, 2H),
3.05 (s, 3H), 3.46 (q, 2H), 3.95 (s, 3H), 6.74 (t, 1H), 7.38 (dd,
1H), 7.65 (s, 1H), 8.00 (t, 1H).
<Preparative Example 42> Preparation of
N.sup.1-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (g); and
N.sup.1-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (h)
mixture
##STR00653## ##STR00654##
[1723] Step 1: Preparation of
2,3-dichloro-6-methoxy-7-(2-morpholine-4-yl-ethoxy)-quinoxaline
[1724] Mass (M+H.sup.+): 358.0
[1725] .sup.1H NMR (500 MHz, DMSO-d6): .delta.2.46 (s, 4H), 2.74
(m, 2H), 3.54 (m, 4H), 3.94 (s, 3H), 4.26 (m, 2H), 7.37 (s, 1H),
7.41 (s, 1H).
Step 2: Preparation of
{4-[3-chloro-7-methoxy-6-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino-
]-butyl}carbamic acid-tert-butylester (a) and
{4-[3-chloro-6-methoxy-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylamino-
]-butyl}carbamic acid-tert-butylester (b) mixture
[1726] Mass (M+H.sup.+): .delta.10.2
Step 3: Preparation of
{4-[3-hydrazino-7-methoxy-6-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylam-
ino]butyl}carbamic acid-tert-butylester (c) and
{4-[3-hydrazino-6-methoxy-7-(2-morpholine-4-yl-ethoxy)-quinoxaline-2-ylam-
ino]butyl}carbamic acid-tert-butylester (d) mixture
[1727] Mass (M+H.sup.+): 506.1
Step 4: Preparation of
{4-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3,--
a]quinoxaline-4-ylamino]butyl}carbamic acid-tert-butylester (e) and
{4-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3,--
a]quinoxaline-4-ylamino]butyl}carbamic acid-tert-butylester (f)
mixture
[1728] Mass (M+H.sup.+): 530.3
Step 5: Preparation of
N.sup.1-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (g) and
N.sup.1-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (h)
mixture
[1729] Mass (M+H.sup.+): 430.1
<Example 576> Preparation of
N-{4-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl butyramide
##STR00655##
[1731] 0.17 g of a target compound was obtained (22% yield) by the
same manner as described in Example 37, except that
N.sup.1-[7-methoxy-1-methyl-8-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (g) and
N.sup.1-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[-
4,3-a]quinoxaline-4-yl]-butane-1,4-diamine dihydrochloride (h)
mixture prepared in step 5 of Preparative Example 42 was used.
[1732] Mass (M+H.sup.+): 514.3
[1733] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44
(s, 2H), 1.62 (m, 4H), 1.87 (m, 3H), 2.48 (s, 2H), 3.04 (m, 5H),
3.47 (m, 2H), 3.56 (s, 4H), 3.83 (s, 3H), 4.20 (t, 2H), 7.10 (s,
1H), 7.52 (s, 1H), 7.7 (t, 1H), 7.81 (t, 1H).
<Example 577> Preparation of
N-{4-[8-methoxy-1-methyl-7-(2-morpholine-4-yl-ethoxy)-[1,2,4]triazolo[4,3-
-a]quinoxaline-4-ylamino]-butyl}-3-methyl butyramide
##STR00656##
[1735] 0.42 g of a target compound was obtained (55% yield) by
separating the structural isomer produced in the preparation
process of Example 576.
[1736] Mass (M+H.sup.+): 514.3
[1737] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (d, 6H), 1.44
(s, 2H), 1.62 (m, 4H), 1.87 (m, 3H), 2.70 (t, 2H), 3.03 (m, 5H),
3.50 (m, 2H), 3.56 (t, 4H), 3.87 (s, 3H), 4.14 (m, 2H), 7.13 (s,
1H), 7.51 (s, 1H), 7.70 (t, 1H), 7.81 (t, 1H)
<Preparative Example 43> Preparation of
{4-[7-(3,5dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]butyl-
}carbamic acid-tert-butylester (c) and
{4-[6-(3,5-dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]buty-
l}carbamic acid-tert-butylester (d)
##STR00657##
[1738] Step 1: Preparation of
2,3-dichloro-6-(3,5-dimethyl-isoxazol-4-yl)-quinoxaline
[1739] Mass (M+H.sup.+): 294.0
[1740] .sup.1H NMR (500 MHz, DMSO-d6) .delta.2.29 (s, 3H), 2.47 (s,
3H), 7.97 (dd, 1H), 8.10 (s, 1H), 8.14 (d, 1H).
Step 2: Preparation of
{4-[3-chloro-7-(3,5-dimethyl-isoxazol-4-yl)-quinoxaline-2-ylamino]-butyl}-
carbamic acid-tert-butylester (a) and
{4-[3-chloro-6-(3,5-dimethyl-isoxazol-4-yl)-quinoxaline-2-ylamino]-butyl}-
carbamic acid-tert-butylester (b)
[1741] Mass (M+H.sup.+): 446.1
[1742] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.42
(m, 2H), 1.59 (m, 2H), 2.23 (s, 3H), 2.42 (s, 3H), 2.92 (q, 2H),
3.44 (m, 2H), 6.74 (d, 1H), 7.36 (dd, 1H) 7.52 (t, 1H), 7.59 (m,
4H), 7.67 (dd, 1H), 7.71 (s, 1H), 7.78 (d, 1H)
Step 3: Preparation of
{4-[7-(3,5dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]butyl-
}carbamic acid-tert-butylester (c) and
{4-[6-(3,5-dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]buty-
l}carbamic acid-tert-butylester (d) mixture
[1743] Mass (M+H.sup.+): 442.3
<Example 578> Preparation of
{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00658##
[1745] 0.34 g of a target compound was obtained (39% yield) by the
same manner as described in step 3 of Preparative Example 5 using
{4-[7-(3,5dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]butyl-
}carbamic acid-tert-butylester (c) and
{4-[6-(3,5-dimethyl-isoxazol-4-yl)-3-hydrazino-quinoxaline-2-ylamino]buty-
l}carbamic acid-tert-butylester (d) mixture (1.74 g, 3.95 mmol)
prepared in step 3 of Preparative Example 43.
[1746] Mass (M+H.sup.+): 466.3
[1747] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.44
(m, 2H), 1.62 (m, 2H), 2.28 (s, 3H), 2.46 (s, 3H), 2.93 (q, 2H),
3.01 (s, 3H), 3.53 (q, 2H), 6.75 (t, 1H), 7.45 (d, 1H), 7.64 (d,
1H), 7.93 (s, 1H), 8.18 (t, 1H).
<Example 579> Preparation of
N.sup.1-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00659##
[1749] 0.4 g of a target compound was obtained (93% yield) by the
same manner as described in Example 58, except that
{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester (0.34 g, 0.73
mmol) prepared in Example 578 was used.
[1750] Mass (M+H.sup.+): 366.2
[1751] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.61 (m, 2H), 1.71
(m, 2H), 2.25 (s, 3H), 2.47 (s, 3H), 2.82 (q, 2H), 3.02 (s, 3H),
3.57 (q, 2H), 7.46 (d, 1H), 7.64 (br, 2H), 7.66 (s, 1H), 7.95 (d,
1H), 8.29 (t, 1H).
<Example 580> Preparation of
N-{4-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quino-
xaline-4-ylamino]-butyl}-3-methyl-butyramide
##STR00660##
[1753] 72 mg of a target compound was obtained (95% yield) by the
same manner as described in Example 37, except that
N.sup.1-[8-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]qu-
inoxaline-4-yl]-butane-1,4-diamine ditrifluoroacetic acid prepared
in Example 579 was used.
[1754] Mass (M+H.sup.+): 450.1
[1755] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.79 (d, 6H), 1.45 (m,
2H), 1.64 (m, 2H), 1.86 (m, 2H), 1.88 (m, 1H), 2.28 (s, 3H), 2.47
(s, 3H), 3.01 (s, 3H), 3.04 (q, 2H), 3.53 (q, 2H), 7.45 (d, 1H),
7.63 (d, 1H), 7.70 (t, 1H), 7.94 (s, 1H), 8.19 (t, 1H).
[1756] The compounds prepared by the same manner as described in
Example 580 are shown in Table 41.
TABLE-US-00041 TABLE 41 Example Structure Name Data Example 581
##STR00661## N-{4-[8- (3,5- dimethyl- isoxazol-4- yl)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino]- butyl}-2- Mass (M
+ H.sup.+): 466.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.68 (d,
3H), 0.83 (d, 3H), 1.48 (m, 2H), 1.63 (m, 2H), 1.90 (m, 1H), 2.28
(s, 3H), 2.46 (s, 3H), (R)-hydroxy- 3.01 (s, 3H), 3-methyl- 3.14
(q, 2H), butyramide 3.53 (q, 2H), 3.60 (m, 1H), 5.23 (d, 1H), 7.45
(d, 1H), 7.64 (d, 1H), 7.67 (t, 1H), 7.93 (s, 1H), 8.19 (t, 1H).
Example 582 ##STR00662## N-{4-[8- (3,5- dimethyl- isoxazol-4-
yl)-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino]-
butyl}-2- Mass (M + H.sup.+): 466.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.68 (d, 3H), 0.83 (d, 3H), 1.48 (m, 2H), 1.63 (m,
2H), 1.90 (m, 1H), 2.28 (s, 3H), 2.46 (s, 3H), (S)-hydroxy- 3.01
(s, 3H), 3-methyl- 3.13 (q, 2H), butyramide 3.53 (q, 2H), 3.60 (m,
1H), 5.23 (d, 1H), 7.45 (d, 1H), 7.63 (d, 1H), 7.65 (t, 1H), 7.93
(s, 1H), 8.19 (t, 1H).
<Example 583> Preparation of
{4-[7-(3,5-dimethyl-isoxazol-4-yl)-1-methyl-[1,2,4]triazolo[4,3-a]quinoxa-
line-4-ylamino]-butyl}-carbamic acid-tert-butylester
##STR00663##
[1758] 0.38 g of a target compound was obtained (44% yield) by
separating the structural isomer produced in the preparation
process of Example 578.
[1759] Mass (M+H.sup.+): 466.3
[1760] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.30 (s, 9H), 1.43 (m,
2H), 1.61 (m, 2H), 2.22 (s, 3H), 2.41 (s, 3H), 2.93 (q, 2H), 3.01
(s, 3H), 3.53 (q, 2H), 6.75 (t, 1H), 7.25 (d, 1H), 7.52 (s, 1H),
8.12 (d, 1H), 8.17 (t, 1H).
[1761] The compounds prepared by the same manner as described in
Example 583 are shown in Table 42.
TABLE-US-00042 TABLE 42 Example Structure Name Data Example 584
##STR00664## N.sup.1-[7-(3,5- dimethyl- isoxazol-4- yl)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-yl]- butane-1,4- diamine
Mass (M + H.sup.+): 366.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.61 (m, 2H), 1.69 (m, 2H), 2.23 (s, 3H), 2.41 (s, 3H), 2.83
(q, 2H), 3.02 (s, 3H), 3.56 (q, 2H), ditrifluoro- 7.29 (d, 1H),
acetic acid 7.52 (s, 1H), 7.63 (br, 2H), 8.15 (d, 1H), 8.32 (t,
1H). Example 585 ##STR00665## N-{4-[7- (3,5- dimethyl- isoxazol-4-
yl)-1- methyl- [1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino]-
butyl}-3- Mass (M + H.sup.+): 450.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.77 (d, 6H), 1.44 (m, 2H), 1.64 (m, 2H), 1.86 (m,
2H), 1.88 (m, H), 2.23 (s, 3H), 2.41 (s, 3H), methyl- 3.01 (s, 3H),
butyramide 3.05 (q, 2H), 3.52 (q, 2H), 7.26 (d, 1H), 7.52 (s, 1H),
7.70 (t, 1H), 8.13 (d, 1H), 8.19 (t, 1H). Example 586 ##STR00666##
N-{4-[7- (3,5- dimethyl- isoxazol-4- yl)-1- methyl- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino]- butyl}-2- (R)-hydroxy- Mass (M +
H.sup.+): 466.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.66 (d,
3H), 0.81 (d, 3H), 1.48 (m, 2H), 1.63 (m, 2H), 1.89 (m, 1H), 2.23
(s, 3H), 2.41 (s, 3H), 3.01 (s, 3H), 3-methyl- 3.13 (q, 2H),
butyramide 3.52 (q, 2H), 3.60 (m, 1H), 5.23 (d, 1H), 7.26 (d, 1H),
7.52 (s, 1H), 7.65 (t, 1H), 8.13 (d, 1H), 8.19 (t, 1H). Example 587
##STR00667## N-{4-[7- (3,5- dimethyl- isoxazol-4- yl)-1- methyl-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino]- butyl}-2-
(S)-hydroxy- Mass (M + H.sup.+): 466.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.66 (d, 3H), 0.82 (d, 3H), 1.47 (m, 2H), 1.63 (m,
2H), 1.88 (m, 1H), 2.23 (s, 3H), 2.41 (s, 3H), 3.01 (s, 3H),
3-methyl- 3.13 (q, 2H), butyramide 3.52 (q, 2H), 3.60 (m, 1H), 5.23
(d, 1H), 7.26 (d, 1H), 7.52 (s, 1H), 7.65 (t, 1H), 8.13 (d, 1H),
8.19 (t, 1H).
<Example 588> Preparation of
N.sup.1-[7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
yl]-butane-1,4-diamine ditrifluoroacetic acid
##STR00668##
[1763]
[4-(3-Hydrazino-7-methoxy)-quinoxaline-2-ylamino)butyl]-carbamic
acid-tert-butylester (0.95 g, 2.2 mmol) prepared in step 2 of
Preparative Example 20 was dissolved in trifluoroacetic acid,
followed by reflux stirring for 3 hours. Upon completion of the
reaction, acid was eliminated by distillation under reduced
pressure, followed by recrystallization with methanol and ether. As
a result, 1 g of a target compound was obtained (68% yield).
[1764] Mass (M+H.sup.+): 355.1
<Example 589> Preparation of
[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butyl]-carbamic acid isopropylester
##STR00669##
[1766] 0.03 g of a target compound was obtained (21% yield) by the
same manner as described in Example 60, except that
N.sup.1-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butane-1,4-diamine ditrifluoroacetic acid prepared in
Example 588 was used.
[1767] Mass (M+H.sup.+): 441.2
[1768] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.10 (d, 6H), 1.45 (m,
2H), 1.62 (m, 2H), 2.99 (m, 2H), 3.50 (q, 2H), 3.80 (s, 3H), 4.68
(m, 1H), 6.99 (d, 1H), 7.13 (s, 1H), 7.70 (t, 1H), 7.73 (d, 1H),
8.51 (t, 1H).
<Example 590> Preparation of
N-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yla-
mino)-butyl]-3-methyl-butyramide
##STR00670##
[1770] 0.04 g of a target compound was obtained (33% yield) by the
same manner as described in Example 74, except that
N.sup.1-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butane-1,4-diamine ditrifluoroacetic acid prepared in
Example 588 was used.
[1771] Mass (M+H.sup.+): 439.2
[1772] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.46 (m,
2H), 1.64 (m, 2H), 1.86 (m, 2H), 1.87 (m, 1H), 3.04 (q, 2H), 3.54
(q, 2H), 3.82 (s, 3H), 6.98 (d, 1H), 7.12 (s, 1H), 7.71 (t, 1H),
7.73 (d, 1H), 8.51 (t, 1H).
<Example 591> Preparation of 3-methyl-pentanoic
acid-[4-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butyl]-amide
##STR00671##
[1774] 0.06 g of a target compound was obtained (37% yield) by the
same manner as described in Example 73, except that
N.sup.1-(7-methoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4--
ylamino)-butane-1,4-diamine ditrifluoroacetic acid prepared in
Example 588 was used.
[1775] Mass (M+H.sup.+): 453.2
[1776] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.79 (m, 6H),
1.08-1.25 (brm, 2H), 1.46 (m, 2H), 1.63 (m, 2H), 1.78 (m, 2H), 1.96
(m, 1H), 3.06 (q, 2H), 3.50 (q, 2H), 3.81 (s, 3H), 6.98 (d, 1H),
7.12 (s, 1H), 7.71 (t, 1H), 7.73 (d, 1H), 8.51 (t, 1H).
<Example 592> Preparation of
N.sup.1-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxalin-
e-4-yl)-butane-1,4-diamine ditrifluoroacetic acid
##STR00672##
[1778] 0.35 g of a target compound was obtained (18% yield) by the
same manner as described in Example 558, except that
[4-(3-hydrazino-7,8-dimethoxy)-quinoxaline-2-ylamino)butyl]-carbamic
acid-tert-butylester was used.
[1779] Mass (M+H.sup.+): 385.2
[1780] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.61 (m, 2H), 1.70
(m, 2H), 2.82 (q, 2H), 3.53 (brs, 3H), 3.57 (q, 2H), 3.81 (s, 3H),
3.86 (s, 3H), 7.17 (s, 1H), 7.24 (s, 1H), 7.67 (brs, 3H), 8.31 (t,
1H).
<Example 593> Preparation of
N-[4-(7,8-dimethoxy-1-trifluoromethyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-
-ylamino)-butyl]-3-methyl-butyramide
##STR00673##
[1782] 0.21 g of a target compound was obtained (93% yield) by the
same manner as described in Example 66, except that
N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylami-
no)-butane-1,4-diamine ditrifluoroacetic acid was used.
[1783] Mass (M+H.sup.+): 469.2
[1784] .sup.1H NMR (500 MHz, DMSO-d6) .delta.0.80 (d, 6H), 1.47 (m,
2H), 1.64 (m, 2H), 1.87 (d, 2H), 1.90 (m, 1H), 3.04 (q, 2H), 3.52
(q, 2H), 3.86 (s, 3H), 3.94 (s, 3H), 7.18 (s, 1H), 7.23 (s, 1H),
7.70 (t, 1H), 8.27 (t, 1H).
<Preparative Example 44> Preparation of
4-chloro-7,8-dimethoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00674##
[1786] 1.02 g of a target compound was obtained (89% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that (3-chloro-6,7-dimethoxy-quinoxaline-2-yl)-hydrazine (1 g, 3.92
mmol) prepared in step 2 of Preparative Example 5 and 6 ml of
triethylorthopropionate were used.
[1787] Mass (M+H.sup.+): 293.1
[1788] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.49 (t, 3H), 2.47
(q, 2H), 3.27 (s, 3H), 3.88 (s, 3H), 3.98 (s, 3H), 7.52 (s, 1H),
7.60 (s, 1H).
[1789] Examples of the compounds synthesized using
4-chloro-7,8-dimethoxy-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared in Preparative Example 44 are shown in Table 43 below.
TABLE-US-00043 TABLE 43 Example Structure Name Data Example 594
##STR00675## [4-(1- ethyl-7,8- dimethoxy- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- Mass (M +
H.sup.+): 445.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.32 (s,
9H), 1.42 (m, 2H), 1.47 (t, 3H), 1.60 (m, 2H), 2.92 (q, 2H), 3.44
(q, 2H), 3.47 (q, 2H), 3.82 (s, 3H), 3.89 butylester (s, 3H), 6.75
(t, 1H), 7.10 (s, 1H), 7.54 (s, 1H), 7.82 (t, 1H) Example 595
##STR00676## N.sup.1-(1- ethyl-7,8- dimethoxy- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-yl)- butane-1,4- diamine Mass (M + H.sup.+):
345.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.46 (t, 3H), 1.59
(m, 2H), 1.67 (m, 2H), 2.81 (q, 2H), 3.43 (q, 2H), 3.52 (q, 2H),
3.82 (s, 3H), ditrifluoro 3.86 (s, 3H), 7.10 acetic acid (s, 1H),
7.46 (s, 1H), 7.68 (brs, 3H), 7.98 (brs, 1H), Example 596
##STR00677## [4-(1- ethyl-7,8- dimethoxy- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- carbamic acid Mass (M + H.sup.+):
431.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.10 (d, 6H), 1.40
(m, 2H), 1.47 (m, 1H), 1.65 (m, 2H), 2.94 (q, 2H), 3.45 (q, 2H),
3.48 (s, 3H), 3.82 (s, 3H), 3.86 isopropylester (s, 3H), 4.69 (m,
1H), 6.96 (t, 1H), 7.11 (s, 1H), 7.45 (s, 1H), 7.89 (brs, 1H)
Example 597 ##STR00678## N-[4-(1- ethyl-7,8- dimethoxy-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl-
butyramide Mass (M + H.sup.+): 429.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.80 (d, 6H), 1.44 (m, 2H), 1.47 (d, 2H), 1.62 (m,
2H), 1.86 (m, 2H), 1.87 (m, 1H), 3.10 (q, 2H), 3.44 (q, 2H), 3.47
(q, 2H), 3.82 (s, 3H), 3.86 (s, 3H), 7.10 (s, 1H), 7.46 (s, 1H),
7.76 (t, 1H), 7.83 (t, 1H) Example 598 ##STR00679## [4-(1-
ethyl-7,8- dimethoxy- [1,2,4]triazolo [4,3-a] quinoxaline-
4-ylamino)- butyl]- carbamic acid Mass (M + H.sup.+): 445.2;
.sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81 (d, 6H), 1.44 (m, 2H),
1.47 (d, 3H), 1.74 (m, 2H), 1.76 (m, 1H), 3.00 (q, 2H), 3.44 (q,
2H), 3.45 (q, 2H), 3.66 isobutylester (d, 2H), 3.82 (s, 3H), 3.86
(s, 3H), 7.02 (t, 1H), 7.10 (s, 1H), 7.46 (s, 1H), 7.84 (t, 1H)
<Preparative Example 45> Preparation of
4-chloro-7,8-dimethoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00680##
[1791] 1.02 g of a target compound was obtained (89% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that (3-chloro-6,7-dimethoxy-quinoxaline-2-yl)-hydrazine (1 g, 3.92
mmol) prepared in step 2 of Preparative Example 5 and
isovalerylchloride 5 ml of triethylorthoisobutylate were used.
[1792] Mass (M+H.sup.+): 307.2
[1793] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.51 (d, 6H), 3.89
(s, 3H), 3.98 (s, 3H), 4.04 (m, 1H), 7.55 (s, 1H), 7.60 (s,
1H).
[1794] Examples of the compounds synthesized using
4-chloro-7,8-dimethoxy-1-isopropyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared in Preparative Example 45 are shown in Table 44 below.
TABLE-US-00044 TABLE 44 Example Structure Name Data Example 599
##STR00681## [4-(1- isopropyl- 7,8- dimethoxy- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert-
butylester Mass (M + H.sup.+): 459.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.31 (S, 9H), 1.42 (m, 2H), 1.48 (d, 6H), 1.61 (m,
2H), 2.92 (q, 2H), 3.47 (q, 2H), 3.83 (s, 3H), 3.85 (s, 3H), 3.93
(m, 1H), 6.75 (t, 1H), 7.11 (s, 1H) 7.45 (s, 1H) 7.83 (t, 1H).
Example 600 ##STR00682## N.sup.1-(1- isopropyl- 7,8- dimethoxy-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-yl)- butane-1,4- diamine
ditrifluoro Mass (M + H.sup.+): 359.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.47 (d, 6H), 1.59 (m, 2H), 1.67 (m, 2H), 2.82 (q,
2H), 3.53 (q, 2H), 3.83 (s, 3H), 3.94 (m, 1H), 7.11 (s, 1H), 7.46
(s, 1H), 7.63 acetic acid (brs, 3H), 8.02 (brs, 1H). Example 601
##STR00683## [4-(1- isopropyl- 7,8- dimethoxy- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-ylamino)- butyl]- carbamic acid
isopropylester Mass (M + H.sup.+): 445.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.21 (d, 6H), 1.78 (m, 2H), 1.79 (m, 6H), 1.80 (m,
2H), 3.26 (q, 2H), 3.73 (m, 1H), 3.76 (q, 2H), 3.97 (s, 3H), 3.99
(s, 3H), 4.72 (t, 1H), 4.90 (t, 1H) 6.21 (s, 1H), 7.46 (s, 1H).
Example 602 ##STR00684## [4-(1- isopropyl- 7,8- dimethoxy-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]- carbamic
acid isobutylester Mass (M + H.sup.+): 459.2; .sup.1H NMR (500 MHz,
CDCl.sub.3): .delta.0.90 (d, 6H), 1.65 (d, 6H), 1.68 (m, 2H), 1.78
(m, 2H), 1.80 (m, 1H), 3.28 (q, 2H), 3.74 (q, 2H), 3.82 (m, 1H),
3.83 (d, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 4.84 (brs, 1H), 6.30
(brs, 1H), 7.21 (s, 1H), 7.46 (s, 1H). Example 603 ##STR00685##
N-[4-(1- isopropyl- 7,8- dimethoxy- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]-3- methyl- butyramide Mass (M +
H.sup.+): 443.3; .sup.1H NMR (500 MHz, CDCl.sub.3): .delta.0.93 (d,
6H), 1.65 (d, 6H), 1.66 (d, 2H), 1.79 (m, 2H), 2.01 (m, 2H), 2.10
(m, 1H), 3.33 (q, 2H), 3.73 (q, 2H), 3.76 (m, 1H), 3.97 (s, 3H),
3.99 (s, 3H) 5.54 (brs, 1H), 6.19 (brs, 1H), 7.21 (s, 1H), 7.46 (s,
1H).
<Preparative Example 46> Preparation of
4-chloro-7,8-dimethoxy-1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline
##STR00686##
[1796] 1.02 g of a target compound was obtained (89% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that (3-chloro-6,7-dimethoxy-quinoxaline-2-yl)-hydrazine (1 g, 3.92
mmol) prepared in step 2 of Preparative Example 5 and 5 ml of
triethylorthoisobenzoate were used.
[1797] Mass (M+H.sup.+): 341.2
[1798] .sup.1H NMR (500 MHz, DMSO-d6): .delta.3.27 (s, 3H), 3.33
(s, 3H), 7.54 (s, 1H), 7.69 (m, 3H), 7.70 (m, 3H).
[1799] Examples of the compounds synthesized using
4-chloro-7,8-dimethoxy-1-phenyl-[1,2,4]triazolo[4,3-a]quinoxaline
prepared in Preparative Example 46 are shown in Table 45 below.
TABLE-US-00045 TABLE 45 Example Structure Name Data Example 604
##STR00687## [4-(1- phenyl-7,8- dimethoxy- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- carbamic acid-tert- butylester
Mass (M + H.sup.+): 493.4; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.33 (s, 3H), 1.46 (m, 2H), 1.63 (m, 2H), 2.94 (q, 2H), 3.27
(s, 3H), 3.52 (q, 2H), 3.78 (s, 3H), 6.61 (s, 1H), 6.74 (t, 1H),
7.08 (s, 1H), 7.66 (m, 3H) 7.73 (m, 2H), 8.00 (t, 1H). Example 605
##STR00688## N.sup.1-(1- phenyl-7,8- dimethoxy- [1,2,4]triazolo
[4,3-a] quinoxaline- 4-yl)- butane-1,4- diamine ditrifluoro acetic
acid Mass (M + H.sup.+): 393.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.1.64 (m, 2H), 1.71 (m, 2H), 2.84 (q, 2H), 3.24 (s, 3H), 3.37
(brs, 2H), 3.56 (q, 2H), 3.78 (s, 3H), 6.62 (s, 1H), 7.07 (s, 1H),
7.65 (m, 2H), 7.73 (m, 3H) 8.07 (t, 1H). Example 606 ##STR00689##
[4-(1- phenyl-7,8- dimethoxy- [1,2,4]triazolo [4,3- quinoxaline-
4-ylamino)- butyl]- carbamic acid isopropylester Mass (M +
H.sup.+): 479.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.11 (d,
6H), 1.48 (m, 2H), 1.64 (m, 2H), 2.99 (q, 2H), 3.23 (s, 3H), 3.52
(q, 2H), 3.79 (s, 3H), 4.70 (m, 1H), 6.61 (s, 1H), 6.98 (t, 1H),
7.09 (s, 1H) 7.66 (m, 3H), 7.75 (m, 2H), 8.01 (m, 1H). Example 607
##STR00690## [4-(1- phenyl-7,8- dimethoxy- [1,2,4]triazolo [4,3-a]
quinoxaline- 4-ylamino)- butyl]- carbamic acid isobutylester Mass
(M + H.sup.+): 493.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.82
(d, 6H), 1.49 (m, 2H), 1.65 (m, 2H), 1.77 (m, 1H), 3.00 (q, 2H),
3.23 (s, 3H), 3.55 (q, 2H), 3.67 (q, 2H), 3.79 (s, 3H), 6.61 (s,
1H), 7.05 (q, 1H) 7.09 (s, 1H), 7.66 (m, 3H), 7.73 (m, 2H), 8.00
(m, 1H). Example 608 ##STR00691## N-[4-(1- phenyl-7,8- dimethoxy-
[1,2,4]triazolo [4,3-a] quinoxaline- 4-ylamino)- butyl]-3- methyl-
butyramide Mass (M + H.sup.+): 477.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.0.81 (d, 6H), 1.48 (m, 2H), 1.65 (m, 2H), 1.87 (d,
2H), 1.88 (m, 1H), 3.06 (q, 2H), 3.27 (s, 3H), 3.52 (q, 2H), 3.78
(s, 3H), 6.61 (s, 1H), 7.08 (s, 1H) 7.66 (m, 3H), 7.73 (m, 3H),
8.01 (t, 1H).
[1800] Examples of the compounds synthesized by the same manner as
described in Preparative Examples 44-46 are shown in Table 46
below.
TABLE-US-00046 TABLE 46 Example Structure Name Data Example 609
##STR00692## [4- ([1,2,4]tria- zolo[4,3- a]quinoxaline- 4-
ylamino)- butyl]- carbamic acid-tert- butylester Mass (M +
H.sup.+): 357.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s,
9H), 1.43- 1.52 (m, 2H), 1.62-1.72 (m, 2H), 2.94-3.00 (m, 2H),
3.53- 3.59 (m, 2H), 6.79 (t, J = 5.16 Hz, 1H), 7.32 (t, J = 7.26
Hz, 1H), 7.45 (t, J = 7.53 Hz, 1H), 7.60 (d, J = 7.98 Hz, 1H), 8.15
(d, J = 8.04 Hz, 1H), 8.25 (t, J = 5.61 Hz, 1H), 9.95 (s, 1H).
Example 610 ##STR00693## [4-(1- trifluoro- methyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]- carbamic acid-tert-
butylester Mass (M + H.sup.+): 425.2; .sup.1H NMR (300 MHz,
DMSO-d6): .delta.1.44- 1.54 (m, 2H), 1.63-1.73 (m, 2H), 2.94-3.00
(m, 2H), 3.55- 3.61 (m, 2H), 6.78 (t, J = 4.95) Hz, 1H), 7.39- 7.44
(m, 1H), 7.56 (t, J = 7.35) Hz, 1H), 7.71 (dd, J = 8.13, 0.93 Hz,
1H), 7.87 (d, J = 8.28 Hz, 1H), 8.51 (t, J = 5.67 Hz, 1H). Example
611 ##STR00694## N.sup.1-(1- trifluoro- methyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4-yl)- butane-1,4- diamine Mass (M +
H.sup.+): 325.1; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.61- 1.84
(m, 2H), 2.83-2.88 (m, 2H), 3.60-3.64 (m, 2H), 7.42- 7.47 (m, 1H),
7.57-7.72 (m, 4H), 7.89 (d, J = 8.37 Hz, 1H), 8.61 (t, J = 5.64 Hz,
1H). Example 612 ##STR00695## N-[4-(1- trifluoro- methyl-
(1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]-
acetamide Mass (M+H.sup.+): 367.2; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.47- 1.54 (m, 2H), 1.65-1.70 (m, 2H), 1.78 (s, 3H),
3.05-3.11 (m, 2H), 3.55- 3.62 (m, 2H), 7.42 (t, J = 7.26 Hz, 1H),
7.57 (t, J = 7.71 Hz, 1H), 7.71 (d, J = 8.10 Hz, 1H), 7.80- 7.88,
(m, 2H), 8.52 (t, J = 5.61 Hz, 1H). Example 613 ##STR00696##
[4-(1-ethyl- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)-
butyl]- carbamic acid-tert- butylester Mass (M + H.sup.+): 385.2;
.sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H), 1.42- 1.51 (m,
5H), 1.61-1.71 (m, 2H), 2.94-3.00 (m, 2H), 8.11 (t, J = 5.70 Hz,
1H), 3.39-3.46 (m, 2H), 3.51-3.58 (m, 2H), 6.77 (t, J = 4.65 Hz,
1H), 7.27-7.32 (m, 1H), 7.44 (t, J = 7.38 Hz, 1H), 7.59-7.7.62 (m,
1H), 8.04 (d, J = 8.22 Hz, 1H). Example 614 ##STR00697##
N.sup.1-(1-ethyl- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4-yl)-
butane-1,4- diamine Mass (M + H.sup.+): 325.1; .sup.1H NMR (300
MHz, DMSO-d6): .delta.1.49 (t, J = 7.29 Hz, 3H), 1.62-1.78 (m, 4H),
2.83- 2.90 (m, 2H), 3.45 (q, J = 7.32 Hz, 2H), 3.59- 3.65 (m, 2H),
7.34-7.39 (m, 1H), 7.46-7.52 (m, 1H), 7.64- 7.71 (m, 3H), 8.09 (d,
J = 7.95 Hz, 1H), 8.57 (brs, 1H) Example 615 ##STR00698## [4-(1-
isopropyl- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)-
butyl]- carbamic acid-tert- butylester Mass (M + H.sup.+): 399.2;
.sup.1H NMR (300 MHz, DMSO-d6): .delta.1.36 (s, 9H), 1.44- 1.51 (m,
8H), 1.61-1.71 (m, 2H), 2.94-3.00 (m, 2H), 3.51- 3.58 (m, 2H),
3.90-3.99 (m, 1H), 6.79 (t, J = 5.13 Hz, 1H), 7.29-7.35 (m, 1H),
7.45 (t, J = 7.68 Hz, 1H), 7.62 (d, J = 7.83 Hz, 1H), 8.06- 8.13
(m, 2H). Example 616 ##STR00699## N.sup.1-(1- isopropyl-
[1,2,4]tria- zolo[4,3 -a]quinoxaline- 4-yl)- butane-1,4- diamine
Mass (M + H.sup.+): 299.2; .sup.1H NMR (300 MHz, DMSO-d6):
.delta.1.50 (d, J = 6.69 Hz, 6H), 1.55-1.78 (m, 4H), 2.79- 2.90 (m,
2H), 3.54-3.64 (m, 2H), 3.92-4.01 (m, 1H), 7.36- 7.42 (m, 1H), 7.50
(t, J = 7.59 Hz, 1H), 7.67- 7.82 (m, 4H), 8.12 (d, J = 8.19 Hz,
1H), 8.74 (brs, 1H). Example 617 ##STR00700## [4-(1- phenyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 432.8; .sup.1H NMR (300
MHz, DMSO-d6): .delta.1.30 (s, 9H), 1.38- 1.48 (m, 2H), 1.57-1.65
(m, 2H), 2.89-2.95 (m, 2H), 3.49- 3.55 (m, 2H), 6.74 (t, J = 4.86
Hz, 1H), 6.92 (t, J = 7.32 Hz, 1H), 7.08 (d, J = 8.25 Hz, 1H), 7.28
(t, J = 7.35 Hz, 1H), 7.52-7.70 (m, 6H), 8.22 (t, J = 5.64 Hz, 1H).
Example 618 ##STR00701## N.sup.1-(1- phenyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4-yl)- butane-1,4- diamine Mass (M + H.sup.+):
333.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.65- 1.70 (m, 2H),
1.76-1.81 (m, 2H), 2.86-2.92 (m, 2H), 3.66- 3.67 (m, 2H), 7.04-7.08
(m, 1H), 7.17-7.19 (m, 1H), 7.40- 7.43 (m, 1H), 7.65-7.76 (m, 8H),
Example 619 ##STR00702## N-[4-(1- phenyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4- ylamino)- butyl]- acetamide Mass (M + H.sup.+):
375.2; .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.47- 1.57 (m, 2H),
1.67-1.77 (m, 2H), 1.80 (s, 3H), 3.07-3.13 (m, 2H), 3.63- 3.65 (m,
2H), 7.06 (t, J = 7.47 Hz, 1H), 7.16 (d, J = 8.22 Hz, 1H), 7.41 (t,
J = 7.26 Hz, 1H), 7.65- 7.88 (m, 6H), 7.87 (t, J = 5.25 Hz, 1H),
9.00 (brs, 1H). Example 620 ##STR00703## [4-(7- methoxy-1- ethyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]- carbamic
acid-tert- butylester Mass (M + H.sup.+): 415.2; .sup.1H NMR (500
MHz, DMSO-d6): .delta.1.32 (s, 9H), 1.43 (m, 5H), 1.61 (m, 2H),
2.92 (q, 2H), 3.35 (q, 2H), 3.50 (q, 2H), 3.81 (s, 3H), 6.75 (t,
1H), 6.85 (d, 1H), 7.07 (s, 1H), 7.90 (d, 1H), 8.10 (t, 1H).
Example 621 ##STR00704## N.sup.1-(7- methoxy-1- ethyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4-yl)- butane-1,4- diamine ditrifluoro-
acetic acid Mass (M + H.sup.+): 315.1; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.42 (t, 3H), 1.59 (m, 2H), 1.69 (m, 2H), 2.81 (q,
2H), 3.34 (q, 2H), 3.54 (q, 2H), 3.81 (s, 3H), 6.88 (d, 1H), 7.05
(s. 1H), 7.62 (brm, 2H), 7.93 (d, 1H), 8.19 (t, 1H). Example 622
##STR00705## [4-(7- methoxy-1- ethyl- [1,2,4]tria- zolo[4,3-
a]quinoxaline- 4- ylamino)- butyl]-3- methyl- butyramide Mass (M +
H.sup.+): 399.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.80 (d,
6H), 1.41 (t, 3H), 1.45 (m, 2H), 1.63 (m, 2H), 1.87 (m, 2H), 1.94
(m, 1H), 3.05 (q, 2H), 3.34 (m, 2H), 3.50 (q, 2H), 3.81 (s, 3H),
6.85 (d, 1H), 7.06 (s, 1H), 7.69 (t, 1H), 7.90 (s, 1H), 8.10 (t,
1H). Example 623 ##STR00706## [4-(7- methoxy-1- ethyl- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]- carbamic acid
isopropylester Mass (M + H.sup.+): 401.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.10 (d, 6H), 1.41 (t, 3H), 1.45 (m, 2H), 1.62 (m,
2H), 1.76 (m, 1H), 2.97 (q, 2H), 3.35 (m, 2H), 3.50 (q, 2H), 3.81
(s, 3H), 4.68 (m, 1H), 6.85 (d, 1H), 6.95 (t, 1H), 7.06 (s, 1H),
7.90 (s, 1H), 8.09 (t, 1H). Example 624 ##STR00707## [4-(7-
methoxy-1- ethyl- [l,2,4]tria- zolo[4,3- a]quinoxaline- 4-
ylamino)- butyl]- carbamic acid isobutylester Mass (M + H.sup.+):
415.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81 (d, 6H), 1.42
(t, 3H), 1.47 (m, 2H), 1.62 (m, 2H), 1.76 (m, 1H), 2.99 (q, 2H),
3.34 (m, 2H), 3.51 (q, 2H), 3.67 (q, 2H), 3.80 (s, 3H), 6.85 (d,
1H), 7.00 (t, 1H), 7.06 (s, 1H), 7.90 (s, 1H), 8.09 (t, 1H).
Example 625 ##STR00708## [4-(7- methoxy-1- isopropyl- [l,2,4]tria-
zolo[4,3- a]quinoxaline- 4- ylamino)- butyl] - carbamic acid-tert-
butylester Mass (M + H.sup.+): 429.2; .sup.1H NMR (500 MHz,
DMSO-d6): .delta.1.32 (s, 9H), 1.43 (d, 6H), 1.54 (m, 2H), 1.61 (m,
2H), 2.93 (q, 2H), 3.50 (m, 2H), 3.81 (s, 3H), 3.85 (m, 1H), 6.74
(t, 1H), 6.86 (d, 1H), 7.07 (s, 1H), 7.93 (d, 1H), 8.10 (t, 1H).
Example 626 ##STR00709## N.sup.1-(7- methoxy-1- isopropyl-
[1,2,4]tria- zolo[4,3- a]quinoxaline- 4-yl)- butane-1,4- diamine
ditrifluoro- acetic acid Mass (M + H.sup.+): 329.1; .sup.1H NMR
(500 MHz, DMSO-d6): .delta.1.44 (d, 6H), 1.49 (m, 1H), 1.59 (m,
2H), 1.68 (m, 2H), 2.81 (q, 2H), 3.55 (q, 2H), 3.81 (s, 3H), 6.90
(d, 1H), 7.06 (s, 1H), 7.62 (brm, 2H), 7.95 (d, 1H), 8.22 (t, 1H).
Example 627 ##STR00710## [4-(1- isopropyl-7- methoxy- [1,2,4]tria-
zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]-3- methyl- butyramide
Mass (M + H.sup.+): 413.2; .sup.1H NMR (500 MHz, DMSO-d6):
.delta.0.81 (d, 6H), 1.44 (d, 6H), 1.48 (m, 2H), 1.61 (m, 2H), 1.76
(m, 1H), 2.99 (q , 2H), 3.50 (m, 2H), 3.66 (q, 2H), 3.81 (s, 3H),
3.84 (m, 1H), 6.87 (d, 1H), 7.04 (t, 1H), 7.07 (s, 1H), 7.93 (s,
1H), 8.12 (t, 1H). Example 628 ##STR00711## [4-(1- isopropyl-7-
methoxy- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4- ylamino)- butyl]-
carbamic acid isopropyl- ester Mass (M + H.sup.+): 415.2; .sup.1H
NMR (500 MHz, DMSO-d6): .delta.1.10 (d, 6H), 1.44 (d 6H), 1.48 (m,
2H), 1.61 (m, 2H), 2.97 (q, 2H), 3.50 (m, 2H), 3.81 (s, 3H), 3.85
(m, 1H), 4.68 (m, 1H), 6.87 (d, 1H), 6.95 (t, 1H), 7.07 (s, 1H),
7.93 (s, 1H), 8.10 (t, 1H). Example 629 ##STR00712## [4-(1-
isopropyl-7- methoxy- [1,2,4]tria- zolo[4,3- a]quinoxaline- 4-
ylamino)- butyl]- carbamic acid isobutylester Mass (M + H.sup.+):
429.2; .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.81 (d, 6H), 1.44
(d, 6H), 1.48 (m, 2H), 1.61 (m, 2H), 1.76 (m, 1H), 2.99 (q, 2H),
3.50 (m, 2H), 3.66 (q, 2H), 3.81 (s, 3H), 3.84 (m, 1H), 6.86 (d,
1H), 7.03 (t, 1H), 7.07 (s, 1H), 7.93 (s, 1H), 8.12 (t, 1H).
<Example 630> Preparation of
4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butan-1-ol
##STR00713##
[1802] 1.7 g of a target compound was obtained (68% yield) under
the same conditions except that
4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (2 g, 9.15
mmol) prepared in step 2 of Preparative Example 1 and
4-aminobutanol (1 ml, 11.0 mmol) instead of
tert-butyl(4-aminobutyl) carbamate.
[1803] Mass (M+H.sup.+): 272.1
[1804] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.47 (p, 2H), 1.66 (p,
2H), 2.99 (s, 3H), 3.40 (q, 2H), 3.51 (q, 2H), 4.36 (t, 1H), 7.26
(t, 1H), 7.40 (t, 1H), 7.56 (d, 1H), 8.06 (m, 2H).
<Example 631> Preparation of 2,2-dimethyl-propionic
acid-4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butylester
##STR00714##
[1806] 25 mg of a target compound was obtained (10% yield) by the
same manner as described in Example 59, except that
4-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-butane-1-ol
(200 mg, 0.74 mmol) prepared in Example 630 was used.
[1807] Mass (M+H.sup.+): 356.1
[1808] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.08 (s, 9H), 1.64 (m,
2H), 1.71 (m, 2H), 2.99 (s, 3H), 3.53 (q, 2H), 4.03 (q, 2H), 7.27
(t, 1H), 7.41 (t, 1H), 7.55 (d, 1H), 8.06 (d, 1H), 8.14 (t,
1H).
[1809] The compounds shown in Table 47 below were prepared by the
same manner as described in Example 631.
TABLE-US-00047 TABLE 47 Example Structure Name Data Example 632
##STR00715## isobutyric acid-4-(1- methyl- [1,2,4]tria- zolo[4,3-
a]quinoxal- ine-4- ylamino)- butyl]- ester Mass (M + H.sup.+):
342.1; .sup.1H NMR (500 MHz,DMSO-d6): .delta.1.03 (d, 6H), 1.64 (m,
2H), 1.69 (m, 2H), 2.99 (s, 3H), 3.53 (q, 2H), 4.03 (q, 2H), 4.68
(t, 1H), 7.26 (t, 1H), 7.40 (t, 1H), 7.55 (d, 1H), 8.06 (d, 2H),
8.13 (t, 1H) Example 633 ##STR00716## 3,3- dimethyl- butyric
acid-4-(1- methyl- [1,2,4]tria- zolo[4,3- a]quinoxal- ine-4-
ylamino)- butyl]- ester Mass (M + H.sup.+): 370.2; .sup.1H NMR (500
MHz,DMSO-d6): .delta.0.90 (s, 9H), 1.64 (m, 2H), 1.70 (m, 2H), 2.11
(s, 1H), 2.99 (s, 3H), 3.53 (q, 2H), 4.03 (q, 2H), 7.27 (t, 1H),
7.41 (t, 1H), 7.55 (d, 1H), 8.06 (d, 1H), 8.14 (t, 1H). Example 634
##STR00717## benzoic acid-4-(1- methyl- [1,2,4]tria- zolo[4,3-
a]quinoxal- ine-4- ylamino)- butylester Mass (M + H.sup.+): 376.2;
.sup.1H NMR (500 MHz,DMSO-d6): .delta.1.77 (m, 2H), 1.82 (m, 2H),
2.98 (s, 3H), 3.58 (q, 2H), 4.31 (q, 2H), 7.26 (t, 1H), 7.43 (m,
1H), 7.45 (d, 2H), 7.52 (t, 1H), 7.59 (t, 1H), 7.89 (d, 2H), 8.04
(d, 1H), 8.16 (t, 1H). Example 635 ##STR00718## 4-chloro- benzoic
acid-4-(1- methyl- [1,2,4]tria- zolo[4,3- a]quinoxal- ine-4-
ylamino)- butyl- ester Mass (M + H.sup.+): 410.2; .sup.1H NMR (500
MHz,DMSO-d6): .delta.1.79(brm, 4H), 2.99 (s, 3H), 3.58 (q, 2H),
4.31 (q, 2H), 7.26 (m, 1H), 7.38 (t, 1H), 7.48 (d, 2H), 7.51 (t,
1H), 7.87 (d, 2H), 8.03 (d, 1H), 8.16 (t, 1H). Example 636
##STR00719## 2,3- dichloro- benzoic acid-4-(1- methyl- [1,2,4]tria-
zolo[4,3- a]quinoxal- ine-4- ylamino)- butylester Mass (M +
H.sup.+): 444.1; .sup.1H NMR (500 MHz,DMSO-d6): .delta.1.79(brm,
4H), 2.99 (s, 3H), 3.57 (q, 2H), 4.34 (q, 2H), 7.26 (t, 1H), 7.39
(m, 2H), 7.53 (d, 2H), 7.65 (d, 1H), 7.78 (d, 1H), 8.03 (d, 1H),
8.16 (t, 1H) Example 637 ##STR00720## 2-chloro- benzoic acid-4-(1-
methyl- [1,2,4]tria- zolo[4,3- a]quinoxal- ine-4- ylamino)-
butylester Mass (M + H.sup.+): 410.2; .sup.1H NMR (500
MHz,DMSO-d6): .delta.1.78(brm, 4H), 2.99 (s, 3H), 3.57 (q, 2H),
4.32 (q, 2H), 7.26 (t, 1H), 7.41 (m, 2H), 7.51 (m, 3H), 7.73 (d,
1H), 8.05 (d, 1H), 8.16 (t, 1H).
<Preparative Example 47> Preparation of
[4-(3-hydrazino-7-methoxy-quinoxaline-2-yloxy)-butyl]-carbamic
acid-tert-butylester
##STR00721##
[1810] Step 1: Preparation of
[4-(3-chloro-7-methoxy-quinoxaline-2-yloxy)-butyl]-carbamic
acid-tert-butylester
[1811] 2,3-Dichloro-6-methoxy-quinoxaline (2 g, 8.73 mmol) prepared
in step 1 of Preparative Example 8 was dissolved in 20 ml of
dimethylsulfoxide, to which cesiumcarbonate (4.2 g, 13.1 mmol, 1.5
eq) and (4-hydroxy-butyl)-carbamic acid-tert-butyl ester (1.98 g,
10.48 mmol, 1.2 eq) were added stepwise, followed by stirring at
40-50.degree. C. for 18 hours. Upon completion of the reaction, the
temperature was lowered to room temperature, and the reactant was
extracted with water and ethylacetate. The organic layer was dried
over anhydrous magnesium sulfate to eliminate moisture, followed by
distillation under reduced pressure. The reactant was purified by
column chromatography, and as a result, 1.79 g of a target compound
was obtained (54% yield).
[1812] Mass (M+H.sup.+): 382.2
[1813] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.33 (s, 9H), 1.54 (m,
2H), 1.77 (m, 2H), 2.97 (q, 2H), 3.88 (s, 3H), 4.43 (t, 2H), 6.81
(t, 1H), 7.19 (s, 1H), 7.23 (d, 1H), 7.77 (d, 1H).
Step 2: Preparation of
[4-(3-hydrazino-7-methoxy-quinoxaline-2-yloxy)-butyl]-carbamic
acid-tert-butylester
[1814] [4-(3-Chloro-7-methoxy-quinoxaline-2-yloxy)-butyl]-carbamic
acid-tert-butylester (1.7 g, 4.45 mmol) prepared in step 1 of
Preparative Example 47 and hydrazine hydrate (6.48 ml, 133 mmol, 30
eq) were dissolved in 20 ml of 1,4-dioxane, followed by reflux
stirring for 5 hours. Upon completion of the reaction, the solvent
was distilled under reduced pressure. The reactant was extracted
with ethylacetate and water. The extract was dried over magnesium
sulfate to eliminate moisture, followed by filtering, distillation
and drying under reduced pressure. As a result, 13.5 g of a target
compound was obtained (94% yield), which proceeded to the next
reaction without purification.
[1815] Mass (M+H.sup.+): 378.2
[1816] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.34 (s, 9H), 1.54 (m,
2H), 1.72 (m, 2H), 2.96 (q, 2H), 3.78 (s, 3H), 4.35 (br, 2H), 4.37
(t, 2H), 6.79 (t, 1H), 6.99 (d, 1H), 7.02 (d, 1H), 7.44 (d, 1H),
8.01 (s, 1H).
<Example 638> Preparation of
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-ca-
rbamic acid-tert-butylester
##STR00722##
[1818] 1.34 g of a target compound was obtained (77% yield) by the
same manner as described in step 3 of Preparative Example 5, except
that [4-(3-hydrazino-7-methoxy-quinoxaline-2-yloxy)-butyl]-carbamic
acid-tert-butylester (1.6 g, 4.32 mmol) prepared in step 2 of
Preparative Example 47 was used.
[1819] Mass (M+H.sup.+): 302.2
[1820] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.75 (m, 2H), 1.89
(m, 2H), 2.89 (q, 2H), 2.99 (s, 3H), 3.85 (s, 3H), 4.57 (q, 2H),
7.13 (d, 1H), 7.24 (s, 1H), 7.77 (br, 2H), 8.11 (d, 1H)
<Example 639> Preparation of
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butylami-
ne ditrifluoroacetic acid
##STR00723##
[1822] 1.4 g of a target compound was obtained (78% yield) by the
same manner as described in Example 58, except that
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-ca-
rbamic acid-tert-butylester (1.23 g, 3.26 mmol) prepared in Example
638 was used.
[1823] Mass (M+H.sup.+): 302.2
[1824] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.75 (m, 2H), 1.89
(m, 2H), 2.89 (q, 2H), 2.99 (s, 3H), 3.85 (s, 3H), 4.57 (q, 2H),
7.13 (d, 1H), 7.24 (s, 1H), 7.77 (br, 2H), 8.11 (d, 1H).
<Example 640> Preparation of
N-[4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butyl-
]-3-methyl-butyramide
##STR00724##
[1826] 0.3 g of a target compound was obtained (82% yield) by the
same manner as described in Example 37, except that
4-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yloxy)-butylami-
ne ditrifluoroacetic acid (0.5 g, 0.94 mmol) prepared in Example
639 was used.
[1827] Mass (M+H.sup.+): 386.2
[1828] .sup.1H NMR (500 MHz, DMSO-d6): .delta.0.82 (d, 6H), 1.57
(m, 2H), 1.82 (m, 2H), 1.90 (m, 2H), 1.92 (m, 1H), 2.99 (s, 3H),
3.11 (q, 2H), 3.84 (s, 3H), 4.55 (q, 2H), 7.10 (d, 1H), 7.25 (s,
1H), 7.77 (t, 1H), 8.10 (d, 1H).
<Example 641> Preparation of
tert-butyl-{2-[(1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-yl)amino]-pe-
ntyl}-carbamate
##STR00725##
[1830] A target compound was obtained (71% yield) by the same
manner as described in Example 1, except that
4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline prepared in
step 2 of Preparative Example 1 and
tert-butyl-(4-aminopentyl)carbamate were used.
[1831] Mass (M+H.sup.+): 385.2
[1832] .sup.1H NMR (300 MHz, DMSO-d6): .delta.1.34-1.45 (m, 13H),
1.61-1.68 (m, 2H), 2.87-2.94 (m, 2H), 3.49-3.56 (m, 2H), 3.02 (s,
3H), 6.76 (t, J=4.59 Hz, 1H), 7.26-7.31 (m, 1H), 7.43 (t, J=7.47
Hz, 1H), 7.59 (d, J=7.41 Hz, 1H), 8.08 (d, J=7.44 Hz, 2H).
<Example 642> Preparation of
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid-tert-butylester
##STR00726##
[1834] 590 mg of a target compound was obtained (74% yield) by the
same manner as described in Example 57, except that
4-chloro-7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
(500 mg, 1.79 mmol) prepared in step 3 of Preparative Example 5 and
tert-butyl-(4-aminopentyl)carbamate were used.
[1835] Mass (M+H.sup.+): 445.3
[1836] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.31 (s, 9H), 1.32
(m, 2H), 1.39 (m, 2H), 1.61 (m, 2H), 2.88 (q. 2H), 3.03 (s, 3H),
3.46 (q, 2H), 3.81 (s, 3H), 3.86 (s, 3H), 6.72 (t, 1H), 7.09 (s,
1H), 7.51 (s, 1H), 7.78 (t, 1H).
[1837] Examples of the compounds synthesized using
[5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-p-
entyl]-carbamic acid-tert-butylester prepared in Example 642 are
shown in Table 48 below.
TABLE-US-00048 TABLE 48 Example Structure Name Data Example 643
##STR00727## N.sup.1-(7,8-dimethoxy-1-methyl-[1,2,4]tria-zolo[4,3-
a]quinoxal- ine-4-yl)- pentane- 1,5- diamine ditrifluoro- acetic
acid Mass (M + H.sup.+): 345.1; .sup.1H NMR (500 MHz,DMSO-d6):
.delta.1.39 (m, 2H), 1.56 (m, 2H), 1.65 (m, 2H), 2.78 (q, 2H), 3.04
(s, 3H), 3.49 (q, 2H), 3.82(s, 3H), 3.87 (s, 3H), 7.08 (s, 1H),
7.52 (s, 1H), 7.79 (brs, 2H), 7.81 (t, 1H). Example 644
##STR00728## [5-(7,8- dimethoxy- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quinoxal- ine-4- ylamino)- pentyl]- carbamic acid isopropyl-
ester Mass (M + H.sup.+): 431.2; .sup.1H NMR (500 MHz,DMSO-d6):
.delta.1.10 (d, 6H), 1.30 (m, 2H), 1.41 (m, 2H), 1.62 (m, 2H), 2.93
(q, 2H), 3.03 (s, 3H), 3.48 (q, 2H), 3.82 (s, 3H), 3.86 (s, 3H),
4.67 (m, 1H), 6.92 (t, 1H), 7.09 (s, 1H), 7.51 (s, 1H), 7.79 (t,
1H). Example 645 ##STR00729## N-[5-(7,8- dimethoxy- 1-methyl-
[1,2,4]tria- zolo[4,3- a]quinoxal- ine-4- ylamino)- pentyl]- 2,2-
dimethyl- propion- amide Mass (M + H.sup.+): 429.3; .sup.1H NMR
(500 MHz,DMSO-d6): .delta.1.02 (s, 9H), 1.30 (m, 2H), 1.42 (m, 2H),
1.64 (m, 2H), 2.98 (q, 2H), 3.03 (s, 3H), 3.46 (q, 2H), 3.82 (s,
3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.34 (t, 1H), 7.51 (s, 1H), 7.77
(t, 1H).
<Example 646> Preparation of
5-(7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pe-
ntanoic acid-tert-butyl
##STR00730##
[1839] 32 mg of a target compound was obtained (15% yield) by the
same manner as described in Example 57, except that
5-aminopentanoic acid-tert-butylamide
##STR00731##
(1.1 g, 2.7 mmol) was used as a substituent for
4-chloro-7,8-dimethoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
(150 mg, 0.54 mmol) prepared in step 3 of Preparative Example
5.
[1840] Mass (M+H.sup.+): 415.2
[1841] .sup.1H NMR (500 MHz, DMSO-d6): .delta.1.19 (s, 9H), 1.51
(m, 2H), 1.60 (m, 2H), 2.02 (q, 2H), 3.04 (s, 3H), 3.47 (q, 2H),
3.82 (s, 3H), 3.87 (s, 3H), 7.10 (s, 1H), 7.30 (s, 1H), 7.52 (s,
1H), 7.82 (t, 1H).
[1842] The compounds shown in Table 49 below were prepared by the
same manner as described in Example 646.
TABLE-US-00049 TABLE 49 Example Structure Name Data Example 647
##STR00732## 5-(7,8- dimethoxy- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid- isopropyl- amide Mass
(M + H.sup.+): 401.2; .sup.1H NMR (500 MHz,DMSO-d6): .delta.0.98
(d, 6H), 1.53 (m, 2H), 1.60 (m, 2H), 2.04 (t, 2H), 3.03 (s. 3H),
3.47 (q, 2H), 3.82 (m, 1H), 3.87 (s, 3H), 3.89 (s, 3H), 7.10 (s,
1H), 7.51 (s, 1H), 7.58 (t, 1H), 7.90 (brs, 1H). Example 648
##STR00733## 5-(7,8- dimethoxy- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid- isobutyl- amide Mass
(M + H.sup.+): 415.4; .sup.1H NMR (500 MHz,DMSO-d6): .delta.0.77
(d, 6H), 1.51 (m, 1H), 1.59 (m, 2H), 1.61 (d, 2H), 2.11 (q. 2H),
2.81 (q, 2H), 3.04 (s, 3H), 3.48 (m, 2H), 3.82 (s, 3H), 3.87 (s,
3H), 7.10 (s, 1H), 7.52 (s, 1H), 7.70 (t, 1H), 7.81 (t, 1H).
Example 649 ##STR00734## 5-(7,8- dimethoxy- 1-methyl- [1,2,4]tria-
zolo[4,3- a]quinoxal- ine-4- ylamino)- pentanoic acid-(2- methyl-
butyl)- amide Mass (M + H.sup.+): 429.2; .sup.1H NMR (500
MHz,DMSO-d6): .delta.0.75 (d, 3H), 0.77 (t, 3H), 1.01 (m, 1H), 1.39
(m, 2H), 1.56 (m, 2H), 1.59 (m, 2H), 2.09 (q, 2H), 2.81 (m, 2H),
3.04 (s, 3H), 3.48 (q. 2H), 3.82 (s, 3H), 3.87 (s, 3H), 7.10 (s,
1H), 7.52 (s, 1H), 7.66 (t, 1H), 7.82 (t, 1H). Example 650
##STR00735## 5-(7,8- dimethoxy- 1-methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid- (furan-2- ylmethyl)-
amide Mass (M + H.sup.+): 439.2; .sup.1H NMR (500 MHz,DMSO-d6):
.delta.1.58 (m, 4H), 2.13 (m, 2H), 3.07 (s, 3H), 3.48 (q, 2H), 3.82
(q, 2H), 3.87 (s, 3H), 4.20 (d, 2H), 6.16 (d, 1H), 6.30 (d, 1H),
7.10 (s, 1H), 7.49 (s, 1H), 7.52 (s, 1H), 7.80 (t, 1H), 8.20 (t,
1H). Example 651 ##STR00736## 5-(7,8- dimethoxy- 1-methyl-
[1,2,4]tria- zolo[4,3- a]quino- xaline-4- ylamino)- pentanoic acid-
benzylamide Mass (M + H.sup.+): 449.2; .sup.1H NMR (500
MHz,DMSO-d6): .delta.1.60 (m, 2H), 1.63 (m, 2H), 2.18 (q, 2H), 3.04
(s, 3H), 3.51 (q, 2H), 3.81 (s, 3H), 3.87 (s, 3H), 4.22 (d, 2H),
7.10 (s, 1H), 7.18 (m, 3H), 7.19 (m, 2H), 7.53 (s, 1H), 7.83 (t,
1H), 8.25 (t, 1H). Example 652 ##STR00737## 5-(7,8- dimethoxy-
1-methyl- [1,2,4]tria- zolo[4,3- a]quino- xaline-4- ylamino)-
pentanoic acid-(1H- pyrrole-2- ylmethyl)- amide Mass (M + H.sup.+):
438.2; .sup.1H NMR (500 MHz,DMSO-d6): .delta.1.47 (m, 2H), 1.62 (m,
2H), 3.04 (q, 2H), 3.06 (d, 2H), 3.29 (s. 3H), 3.50 (q, 2H), 3.82
(s, 3H), 3.87 (s, 3H), 5.73 (s, 1H), 5.82 (d, 1H), 6.53 (d, 1H),
7.10 (s, 1H), 7.52 (s, 1H), 7.72 (t, 1H), 7.80 (t, 1H), 10.43 (brs,
1H).
<Example 653> Preparation of
5-(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline-4-ylamino)-pentan-
oic acid-tert-butylamide
##STR00738##
[1844] Mass (M+H.sup.+): 385.2
[1845] .sup.1H NMR (500 MHz, DMSO-d6) .delta.1.19 (s, 9H), 1.52 (m,
2H), 1.61 (m, 2H), 2.03 (m, 2H), 2.95 (s, 3H), 3.49 (q, 2H), 3.80
(s, 3H), 6.84 (d, 1H), 7.05 (s, 1H), 7.31 (t, 1H), 7.95 (s, 1H),
8.09 (t, 1H).
[1846] The compounds shown in Table 50 below were prepared by the
same manner as described in Example 653.
TABLE-US-00050 TABLE 50 Example Structure Name Data Example 654
##STR00739## 5-(7- methoxy-1- methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid isopropyl- amide Mass
(M + H.sup.+): 371.2; .sup.1H NMR (500 MHz,DMSO-d6): .delta.0.98
(d, 6H), 1.54 (m, 2H), 1.61 (m, 2H), 2.04 (m, 2H), 2.95 (s, 3H,
3.50 (q, 2H), 3.77 (m, 1H), 3.81 (s, 3H), 6.85 (d, 1H), 7.06 (s,
1H), 7.57 (t, 1H), 7.95 (s, 1H), 8.09 (t, 1H). Example 655
##STR00740## 5-(7- methoxy-1- methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid isobutyl- amide Mass (M
+ H.sup.+): 385.2; .sup.1H NMR (500 MHz,DMSO-d6): .delta.0.76 (d,
6H), 1.54 (m, 1H), 1.58 (m, 2H), 1.62 (m, 2H), 2.10 (m, 2H), 2.81
(m, 2H), 2.95 (s, 3H), 3.50 (q, 2H), 3.81 (s, 3H), 6.84 (d, 1H),
7.05 (s, 1H), 7.71 (t, 1H), 7.94 (s, 1H), 8.09 (t, 1H). Example 656
##STR00741## 5-(7- methoxy-1- methyl- [1,2,4]tria- zolo[4,3-
a]quino- xaline-4- ylamino)- pentanoic acid-(2- methyl- butyl)-
amide Mass (M + H.sup.+): 399.2; .sup.1H NMR (500 MHz,DMSO-d6):
.delta.0.76 (m, 6H), 1.01 (m, 1H), 1.16-1.43 (brm, 2H), 1.55 (m,
2H), 1.60 (m, 2H), 2.09 (m, 2H), 2.81 (m, 2H), 2.95 (s, 3H), 3.50
(q, 2H), 3.81 (s, 3H), 6.84 (d, 1H), 7.05 (s, 1H), 7.66 (t, 1H),
7.94 (s, 1H), 8.09 (t, 1H). Example 657 ##STR00742## 5-7-
methoxy-1- methyl- [1,2,4]tria- zolo[4,3- a]quino- xaline-4-
ylamino)- pentanoic acid- (furan-2- ylmethyl)- amide Mass (M +
H.sup.+): 409.2; .sup.1H NMR (500 MHz,DMSO-d6): .delta.1.61 (m,
2H), 1.64 (m, 2H), 2.14 (m, 2H), 2.95 (s, 3H), 3.51 (q, 2H), 3.81
(s, 3H), 4.20 (d, 2H), 6.15 (t, 1H), 6.30 (t, 1H), 6.85 (d, 1H),
7.06 (s, 1H), 7.49 (s, 1H), 7.96 (d, 1H), 8.09 (t, 1H), 8.20 (t,
1H). Example 658 ##STR00743## 5-(7- methoxy-1- methyl- [1,2,4]tria-
zolo[4,3- a]quino- xaline-4- ylamino)- pentanoic acid benzamide
Mass (M + H.sup.+): 419.2; .sup.1H NMR (500 MHz,DMSO-d6):
.delta.1.63 (m, 4H), 2.17 (m, 2H), 2.95 (s, 3H), 3.51 (m, 2H), 3.80
(s, 3H), 4.21 (d, 2H), 6.85 (d, 1H), 7.05 (d, 1H), 7.15-7.25 (brm,
5H), 7.94 (d, 1H), 8.09 (t, 1H), 8.25 (t, 1H). Example 659
##STR00744## 5-(1- methyl- [1,2,4]tria- zolo[4,3- a]quino-
xaline-4- ylamino)- pentanoic acid isopropyl- amide Mass (M +
H.sup.+): 341.1; .sup.1H NMR (300 MHz,DMSO-d6): .delta.1.02 (t, J =
6.30 Hz, 6H), 1.60-1.66 (m, 4H), 2.09 (t, J = 6.65 Hz, 2H), 3.30
(s, 3H), 3.54-3.55 (m, 2H), 3.79-3.83 (m, 1H), 7.31 (t, J = 7.20
Hz, 1H), 7.45 (t, J = 7.50 Hz, 1H), 7.60-7.63 (m, 2H), 8.09-8.13
(m, 2H). Example 660 ##STR00745## 5-(1- methyl- [1,2,4]tria-
zolo[4,3- a]quino- xaline-4- ylamino)- pentanoic acid isobutyl-
amide Mass (M + H.sup.+): 355.1; .sup.1H NMR (300 MHz,DMSO-d6):
.delta.0.81 (d, J = 6.65 Hz, 6H), 2.12-2.16 (m, 2H), 1.58-1.68 (m,
5H), 3.04 (s, 3H), 2.84-2.86 (m, 2H), 3.53-3.57 (m, 2H), 7.31 (t, J
= 7.70 Hz, 1H), 7.45 (t, J = 7.65 Hz, 1H), 7.61 (d, J = 8.00 Hz,
1H), 7.76 (t, J = 5.40 Hz, 1H), 8.10 (d, J = 8.25 Hz, 1H), 8.14
(brs, 1H). Example 661 ##STR00746## 6-(1- methyl- [1,2,4]tria-
zolo[4,3- a]quino- xaline-4- ylamino)- hexanoic acid isopropyl-
amide Mass (M + H.sup.+): 355.2; .sup.1H NMR (300 MHz,DMSO-d6):
.delta.1.01 (d, J = 6.60 Hz, 6H), 1.30-1.37 (m, 2H), 1.52-1.58 (m,
2H), 1.65-1.71 (m, 2H), 2.02-2.05 (m, 2H), 3.04 (s, 3H), 3.52-3.56
(m, 2H), 3.78-3.84 (m, 1H), 7.31 (t, J = 7.50 Hz, 1H), 7.45 (t, J =
7.70 Hz, 1H), 7.59-7.62 (m, 2H), 8.09-8.12 (m, 2H). Example 662
##STR00747## 6-(1- methyl- [1,2,4]tria- zolo[4,3- a]quino-
xaline-4- ylamino)- hexanoic acid isobutyl- amide Mass (M +
H.sup.+): 369.0; .sup.1H NMR (300 MHz,DMSO-d6): .delta.0.80 (d, J =
6.65 Hz, 6H), 1.31-1.37 (m, 2H), 1.53-1.71 (m, 5H), 2.08-2.10 (m,
2H), 2.83-2.86 (m, 2H), 3.52-3.56 (m, 2H), 3.04 (s, 3H), 7.31 (t, J
= 7.45 Hz, 1H), 7.45 (t, J = 7.65 Hz, 1H), 7.61 (d, J = 7.85 Hz,
1H), 7.73 (t, J = 5.3 Hz, 1H), 8.09-8.12 (m, 2H).
Experimental Example 1: Evaluation of BRD4 binding inhibition
ability
1-1. Experiment Methods
[1847] The following experiment was performed to evaluate the
ability of [1,2,4]triazolo[4,3-a]quinoxaline derivative of the
present invention to inhibit the interaction between BRD4 (BD1+BD2)
bromodomain, one of BET protein family, and tetraacetylated histone
H4 peptide.
[1848] The compound was serially diluted at the ratio of 1:5 in
assay buffer from 10 mM stock in DMSO (initial concentration: 100
.mu.M) on white OptiPlate-384 (PerkinElmer). A mixture comprising
100 nM GST-BRD4 (BD1+BD2) and 100 nM biotinylated acetyl-histone H4
(Lys5,8,12,16) peptide was prepared in assay buffer (50 mM HEPES pH
7.4; 25 mM NaCl; 0.05% Tween 20; 0.1% bovine serum albumin (BSA);
10 mM dithiothreitol (DTT)). After adding 6 .mu.l of the mixture to
the diluent, 6 .mu.l of the pre-mixed AlphaLISA Glutathione
Acceptor Beads and AlphaScreen Streptavidin Donor Beads
(PerkinElmer, 10 .mu.g/ml in assay buffer, respectively) was added
thereto. The samples were incubated in the dark at room temperature
for 30 minutes (shaking at 300 rpm). Then, the signals were
measured with PerkinElmer Envision HTS Multilabel Reader using an
alpha screen protocol of PerkinElmer. Each plate contained the
negative control in which biotinylated acetyl-histone H4 peptide
and GST-BRD4 (BD1+BD2) were replaced by assay buffer. In the case
of using the software GraphPad Prism for calculation, the negative
control point was input as a low standard value. The positive
control (probe molecule l-BET762 containing protein/peptide
mixture) proceeded to pipetting. IC.sub.50 value was determined by
using GraphPad Prism 3.03 software (or an updated version
thereof).
1-2. Experiment Results
[1849] The results are shown in Table 51 below.
[1850] As shown in Table 51, all the compounds of examples of the
present invention demonstrated BRD4 binding inhibition
activity.
[1851] Among them, the compounds of Examples 3, 4, 7, 8, 9, 10, 14,
15, 16, 19, 20, 30, 31, 37, 39, 45, 47, 51, 54, 57, 59, 60, 62, 63,
64, 65, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,
82, 83, 84, 85, 86, 87, 88, 89, 92, 93, 95, 96, 97, 98, 99, 102,
106, 108, 110, 120, 123, 124, 125, 126, 127, 128, 129, 130, 133,
134, 136, 137, 139, 144, 145, 150, 153, 158, 159, 160, 161, 162,
164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 175, 176, 177,
178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190,
191, 192, 196, 197, 201, 202, 203, 210, 211, 212, 215, 216, 217,
218, 220, 222, 223, 224, 226, 227, 228, 229, 230, 231, 232, 233,
234, 235, 236, 237, 238, 239, 240, 241, 245, 246, 247, 249, 250,
251, 253, 254, 257, 258, 266, 267, 268, 272, 273, 274, 275, 279,
280, 281, 284, 285, 286, 288, 289, 290, 292, 293, 294, 295, 296,
297, 298, 299, 300, 301, 302, 305, 307, 309, 310, 311, 312, 313,
315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 327, 328, 329,
330, 332, 333, 335, 336, 339, 340, 343, 344, 345, 346, 347, 350,
358, 363, 365, 366, 367, 368, 369, 370, 371, 372, 373, 375, 376,
377, 378, 379, 380, 381, 382, 383, 384, 385, 388, 389, 390, 391,
392, 393, 394, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405,
406, 407, 408, 409, 410, 411, 413, 414, 415, 418, 420, 422, 423,
424, 425, 426, 427, 428, 430, 432, 434, 435, 436, 437, 438, 439,
440, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 453, 454,
455, 457, 458, 459, 460, 461, 462, 463, 467, 468, 474, 476, 477,
478, 479, 480, 482, 488, 489, 490, 492, 493, 494, 495, 496, 497,
499, 500, 501, 502, 504, 505, 506, 507, 508, 511, 513, 515, 516,
517, 519, 520, 525, 528, 529, 530, 541, 546, 547, 548, 550, 551,
552, 553, 556, 557, 559, 560, 562, 563, 564, 567, 568, 569, 574,
578, 579, 581, 582, 583, 585, 586, 587, 589, 590, 591, 596, 597,
598, 603, 620, 622, 623, 624, 627, 628, 629, 631, 632, 633, 647,
648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 660 and 662
exhibited IC.sub.50 values of 0.05 .mu.M or less, in particular,
the compounds of Examples 10, 30, 37, 39, 62, 79, 81, 83, 126, 137,
161, 173, 176, 191, 220, 222, 226, 227, 228, 229, 233, 234, 236,
237, 240, 241, 254, 257, 281, 284, 298, 299, 302, 309, 318, 320,
324, 344, 358, 367, 368, 371, 372, 382, 383, 388, 389, 391, 392,
393, 396, 398, 399, 400, 403, 407, 409, 413, 420, 422, 428, 435,
440, 444, 448, 458, 479, 480, 490, 493, 496, 499, 501, 559, 564,
579, 582, 583, 585 and 587 showed IC.sub.50 values of 0.01 .mu.M or
less, indicating that they inhibited BRD4 binding significantly at
a very low concentration.
TABLE-US-00051 TABLE 51 BRD4 Example IC.sub.50 (.mu.M) 1 0.074 3
0.028 4 0.035 7 0.020 8 0.024 9 0.040 10 0.005 11 0.058 12 0.058 13
0.057 14 0.041 15 0.027 16 0.044 17 0.051 19 0.036 20 0.043 21
0.057 22 0.081 24 0.067 25 0.055 28 0.096 29 0.098 30 0.008 31
0.031 32 0.089 34 0.081 37 0.008 38 0.097 39 0.006 40 0.069 42
0.056 44 0.072 45 0.040 46 0.073 47 0.042 49 0.061 50 0.077 51
0.038 52 0.070 53 0.060 54 0.050 57 0.020 59 0.034 60 0.012 61
0.056 62 0.007 63 0.012 64 0.020 65 0.022 66 0.013 67 0.019 68
0.038 70 0.044 71 0.018 72 0.021 73 0.015 74 0.028 75 0.028 76
0.038 77 0.022 78 0.020 79 0.005 80 0.028 81 0.010 82 0.012 83
0.002 84 0.014 85 0.027 86 0.017 87 0.027 88 0.018 89 0.047 90
0.063 92 0.041 93 0.039 94 0.057 95 0.036 96 0.015 97 0.024 98
0.047 99 0.021 100 0.069 101 0.051 102 0.019 105 0.060 106 0.028
108 0.017 110 0.035 114 0.091 117 0.064 118 0.054 119 0.079 120
0.034 121 0.055 123 0.042 124 0.029 125 0.031 126 0.004 127 0.046
128 0.033 129 0.017 130 0.036 133 0.034 134 0.019 135 0.061 136
0.058 137 0.006 138 0.051 139 0.040 140 0.052 144 0.038 145 0.047
150 0.048 151 0.052 152 0.096 153 0.016 154 0.078 155 0.077 158
0.018 159 0.024 160 0.028 161 0.004 162 0.024 164 0.037 165 0.026
166 0.020 167 0.040 168 0.016 169 0.041 170 0.038 171 0.026 172
0.040 173 0.004 175 0.026 176 0.002 177 0.050 178 0.017 179 0.035
180 0.017 181 0.017 182 0.022 183 0.011 184 0.030 185 0.019 186
0.022 187 0.024 188 0.025 189 0.017 190 0.028 191 0.010 192 0.034
195 0.069 196 0.032 197 0.028 199 0.058 200 0.071 201 0.026 202
0.044 203 0.042 205 0.075 210 0.018 211 0.034 212 0.035 215 0.022
216 0.031 217 0.016 218 0.025 219 0.068 220 0.009 221 0.062 222
0.001 223 0.017 224 0.013 226 0.004 227 0.001 228 0.007 229 0.003
230 0.013 231 0.014 232 0.033 233 0.002 234 0.006 235 0.011 236
0.002 237 0.0006 238 0.015 239 0.018 240 0.0009 241 0.007 243 0.065
244 0.089 245 0.032 246 0.023 247 0.031 248 0.054 249 0.031 250
0.019 251 0.031 253 0.050 254 0.007 257 0.008 258 0.049 260 0.062
262 0.072 266 0.043 267 0.039 268 0.035 296 0.096 270 0.085 272
0.025 273 0.049 274 0.027 275 0.038 278 0.051 279 0.018 280 0.014
281 0.0004 283 0.051 284 0.009 285 0.017 286 0.030 287 0.067 288
0.015 289 0.012 290 0.023 291 0.097 292 0.024 293 0.040 294 0.015
295 0.033 296 0.027 297 0.027 298 0.004 299 0.007 300 0.015 301
0.016 302 0.008 303 0.063 305 0.041 307 0.022 308 0.058 309 0.008
310 0.042 311 0.043
312 0.018 313 0.033 314 0.056 315 0.036 316 0.041 317 0.031 318
0.010 319 0.011 320 0.004 321 0.012 322 0.014 323 0.035 324 0.007
325 0.071 326 0.064 327 0.018 328 0.043 329 0.035 330 0.029 332
0.017 333 0.018 334 0.060 335 0.016 336 0.033 339 0.046 340 0.023
341 0.071 342 0.056 343 0.036 344 0.010 345 0.013 346 0.022 347
0.018 348 0.100 349 0.055 350 0.033 354 0.056 357 0.062 358 0.007
363 0.016 364 0.098 365 0.013 366 0.016 367 0.005 368 0.010 369
0.014 370 0.014 371 0.007 372 0.002 373 0.020 374 0.091 375 0.021
376 0.044 377 0.039 378 0.014 379 0.017 380 0.013 381 0.014 382
0.005 383 0.003 384 0.041 385 0.049 386 0.078 388 0.006 389 0.002
390 0.022 391 0.005 392 0.009 393 0.003 394 0.034 396 0.007 397
0.029 398 0.001 399 0.001 400 0.001 401 0.012 402 0.018 403 0.010
404 0.015 405 0.014 406 0.014 407 0.007 408 0.013 409 0.009 410
0.012 411 0.019 413 0.001 414 0.016 415 0.046 416 0.052 417 0.060
418 0.049 420 0.002 422 0.003 423 0.027 424 0.025 425 0.028 426
0.017 427 0.017 428 0.004 430 0.022 432 0.050 433 0.061 434 0.021
435 0.008 436 0.018 437 0.031 438 0.037 439 0.038 440 0.009 442
0.016 443 0.013 444 0.010 445 0.013 446 0.012 447 0.021 448 0.005
449 0.027 450 0.019 451 0.013 453 0.024 454 0.011 455 0.031 456
0.075 457 0.025 458 0.008 459 0.030 460 0.012 461 0.015 462 0.016
463 0.016 464 0.061 465 0.072 467 0.023 468 0.022 469 0.055 470
0.063 474 0.044 476 0.034 477 0.020 478 0.044 479 0.005 480 0.009
481 0.051 482 0.020 485 0.059 488 0.035 489 0.030 490 0.009 492
0.013 493 0.005 494 0.014 495 0.012 496 0.010 497 0.038 498 0.098
499 0.010 500 0.040 501 0.009 502 0.030 503 0.063 504 0.034 505
0.026 506 0.015 507 0.011 508 0.029 510 0.057 511 0.034 512 0.065
513 0.019 514 0.060 515 0.024 516 0.040 517 0.038 519 0.049 520
0.024 523 0.054 524 0.069 525 0.011 528 0.015 529 0.031 530 0.034
532 0.075 533 0.067 537 0.093 538 0.069 541 0.037 542 0.061 545
0.065 546 0.031 547 0.049 548 0.045 549 0.056 550 0.021 551 0.012
552 0.021 553 0.024 555 0.065 556 0.031 557 0.013 558 0.057 559
0.007 560 0.037 562 0.032 563 0.037 564 0.009 567 0.013 568 0.028
569 0.011 574 0.040 575 0.051 576 0.052 578 0.030 579 0.005 581
0.024 582 0.010 583 0.005 585 0.005 586 0.024 587 0.007 589 0.046
590 0.029 591 0.028 593 0.092 594 0.076 596 0.019 597 0.018 598
0.018 601 0.056 602 0.058 603 0.034 620 0.016 622 0.020 623 0.005
624 0.016 627 0.023 628 0.048 629 0.016 631 0.047 632 0.044 633
0.024 634 0.091 641 0.058 642 0.056 646 0.056 647 0.029 648 0.027
649 0.023 650 0.018 651 0.023 652 0.027
653 0.016 654 0.011 655 0.011 656 0.012 657 0.016 658 0.026 659
0.075 660 0.036 661 0.078 662 0.039
Experimental Example 2: Measurement of Cytotoxicity to Thymus
Cancer Cells (Ty-82 Cells)
2-1. Experiment Methods
[1852] The following experiment was performed to evaluate the
cytotoxicity of [1,2,4]triazolo[4,3-a]quinoxaline derivative
according to the present invention to thymus cancer cells (Ty-82
cells).
[1853] First, thymus cancer cells (Ty-82 cells) were distributed in
a 96 well plate at the density of 2.5.times.10.sup.4 cells/well. 24
hours later, the plated cells were treated with the compounds of
the present invention dissolved in DMSO at the different
concentrations ranging from 0.01 .mu.M to 10 .mu.M. 72 hours later,
the activities of the compounds were determined using WST-1
reagent.
2-2. Experiment Results
[1854] The results are shown in Table 52 below.
[1855] As shown in Table 52, the compounds of examples of the
present invention demonstrated cytotoxicity against thymus cancer
cells at low concentrations. In particular, the compounds of
Examples 7, 59, 60, 62, 65, 66, 67, 74, 84, 90, 108, 181, 186, 191,
246, 247, 249, 250, 278, 279, 285, 466, 467, 468 and 469 displayed
IC.sub.50 values of 0.5 .mu.M or less, indicating that they had
excellent cytotoxicity at low concentrations.
TABLE-US-00052 TABLE 52 Ty-82 Cytotoxicity Example IC.sub.50
(.mu.M) IBET762 0.5-0.2 OTX015 0.08-0.04 3 0.92 4 0.65 7 0.26 8
0.86 11 0.95 12 0.85 57 0.74 59 0.42 60 0.12 62 0.29 65 0.37 66
0.058 67 0.17 74 0.17 75 0.79 77 0.92 84 0.027 88 0.97 90 0.40 93
0.56 99 0.55 101 0.88 102 0.84 108 0.37 120 0.62 127 0.62 129 0.83
133 0.88 135 0.73 161 0.81 165 0.58 166 0.58 167 0.88 168 0.60 171
0.58 181 0.30 186 0.34 190 0.65 191 0.31 192 0.68 197 0.65 202 0.64
246 0.49 247 0.40 248 0.51 249 0.40 250 0.30 251 0.68 205 0.55 210
0.76 212 0.84 277 0.93 278 0.18 279 0.12 285 0.091 464 0.79 466
0.34 467 0.20 468 0.23 469 0.094 633 0.90 660 0.84
Experimental Example 3: Measurement of Cytotoxicity of
[1,2,4]triazolo[4,3-a]quinoxaline Derivative to Acute Myelogenous
Leukemia Cells (MV-4-11 Cells)
3-1. Experiment Methods
[1856] The following experiment was performed to evaluate the
cytotoxicity of [1,2,4]triazolo[4,3-a]quinoxaline derivative
according to the present invention to acute myelogenous leukemia
cells (MV-4-11 cells).
[1857] Acute myelogenous leukemia cells (MV-4-11 cells) were
distributed in a 96 well plate at the density of 5.times.10.sup.3
cells/well. The plated cells were treated with the compounds of the
present invention dissolved in DMSO at the different concentrations
ranging from 0.01 .mu.M to 10 .mu.M. 72 hours later, the activities
of the compounds were determined using CCK-8 reagent.
3-2. Experiment Results
[1858] The results are shown in Table 53 below.
[1859] As shown in Table 53, the compounds of examples of the
present invention demonstrated cytotoxicity against acute
myelogenous leukemia cells (MV-4-11 cells) at low concentrations.
In particular, the compounds of Examples 37, 60, 62, 63, 64, 65,
66, 67, 71, 73, 74, 77, 78, 79, 81, 84, 85, 86, 128, 160, 161, 166,
168, 176, 177, 180, 181, 185, 187, 188, 189, 190, 191, 199, 219,
222, 223, 224, 227, 228, 229, 233, 234, 236, 240, 254, 255, 256,
278, 279, 280, 281, 284, 285, 286, 287, 288, 289, 290, 292, 302,
307, 308, 309, 310, 318, 319, 322, 323, 327, 328, 329, 330, 332,
333, 335, 336, 340, 341, 342, 343, 344, 345, 346, 347, 349, 350,
352, 356, 357, 365, 366, 368, 369, 371, 372, 381, 383, 388, 389,
391, 393, 406, 411, 420, 426, 432, 436, 437, 438, 439, 442, 443,
444, 445, 446, 451, 454, 463, 466, 467, 468, 469, 480, 490, 492,
493, 494, 495, 496, 499, 500, 501, 507, 515, 520, 529, 550, 551,
552, 553, 555, 556, 558, 559, 560, 561, 567, 574, 576, 577, 584,
648, 649, 651, 652, 655, 656 and 657 displayed IC.sub.50 values of
0.2 .mu.M or less, indicating that they had excellent cytotoxicity
at low concentrations.
TABLE-US-00053 TABLE 53 MV-4-11 Cytotoxicity Example IC.sub.50
(.mu.M) IBET762 0.4-0.2 OTX015 0.06-0.01 1 0.980 10 0.160 11 0.710
37 0.121 39 0.190 57 0.760 59 0.310 60 0.010 61 0.380 62 0.120 63
0.070 64 0.120 65 0.130 66 0.110 67 0.140 68 0.450 70 0.370 71
0.110 72 0.470 73 0.010 74 0.110 75 0.340 76 0.870 77 0.150 78
0.140 79 0.070 81 0.100 83 0.211 84 0.010 85 0.050 86 0.060 88
0.510 90 0.300 93 0.340 95 0.590 96 0.630 97 0.510 98 0.830 99
0.230 102 0.360 105 0.650 106 0.310 108 0.510 117 0.370 124 0.700
128 0.170 135 0.360 137 0.370 138 0.860 140 0.680 150 0.460 151
0.380 153 0.460 158 0.610 159 0.530 160 0.070 161 0.080 162 0.640
164 0.570 165 0.220 166 0.070 167 0.510 168 0.090 169 0.860 170
0.530 172 0.280 173 0.360 175 0.260 176 0.110 177 0.110 178 0.440
179 0.640 180 0.190 181 0.050 183 0.250 185 0.020 186 0.680 187
0.110 188 0.170 189 0.110 190 0.090 191 0.090 192 0.420 196 0.550
199 0.049 215 0.276 216 0.240 217 0.256 218 0.320 219 0.079 220
0.350 222 0.053 223 0.014 224 0.003 226 0.290 227 0.039 228 0.140
229 0.150 230 0.580 233 0.071 234 0.047 235 0.390 236 0.087 237
0.500 238 0.650 239 0.660 240 0.158 244 0.260 245 0.361 252 0.254
253 0.235 254 0.101 255 0.093 256 0.084 257 0.327 258 0.345 259
0.339 265 0.680 266 0.540 267 0.570 268 0.500 271 0.880 272 0.810
273 0.510 274 0.280 275 0.330 277 0.550 278 0.160 279 0.140 280
0.040 281 0.158 282 0.534 283 0.176 284 0.173 285 0.010 286 0.026
287 0.125 288 0.034 289 0.026 290 0.150 291 0.290 292 0.158 293
0.673 294 0.203 298 0.270 299 0.375 300 0.310 302 0.066 307 0.010
308 0.020 309 0.110 310 0.126 311 0.208 312 0.510 313 0.570 315
0.550 316 0.730 318 0.032 319 0.114 320 0.670 321 0.553 322 0.157
323 0.107 327 0.140 328 0.190 329 0.019 330 0.140 332 0.010 333
0.110 335 0.040 336 0.080 340 0.054 341 0.052 342 0.028 343 0.120
344 0.121 345 0.130 346 0.079 347 0.058 349 0.160 350 0.071 351
0.290 352 0.110 353 0.392 354 0.472 356 0.143 357 0.044 358 0.160
365 0.060 366 0.110 367 0.350 368 0.140 369 0.130 370 0.240 371
0.119 372 0.180 373 0.420 375 0.400 378 0.290 379 0.420 380 0.610
381 0.200 382 0.840 383 0.073 388 0.055 389 0.079 391 0.200 393
0.170 396 0.760 398 0.790 399 0.570 400 0.200 403 0.610 406 0.019
407 0.180 408 0.620 409 0.380 410 0.790 411 0.150 413 0.190 414
0.630 415 0.750 420 0.180 422 0.450 426 0.190 430 0.600 432 0.100
433 0.340 435 0.11 436 0.160 437 0.070 438 0.033 439 0.100 440
0.580 442 0.110 443 0.120 444 0.120 445 0.100 446 0.010 449 0.300
450 0.270 451 0.024
452 0.320 453 0.500 454 0.080 458 0.530 461 0.250 462 0.600 463
0.100 465 0.690 466 0.083 467 0.066 468 0.073 469 0.010 470 0.220
476 0.480 479 0.240 480 0.080 483 0.460 484 0.460 490 0.190 492
0.080 493 0.0480 494 0.110 495 0.029 496 0.020 497 0.730 499 0.140
500 0.098 501 0.060 502 0.331 503 0.575 505 0.533 506 0.340 507
0.021 508 0.575 510 0.335 512 0.631 513 0.279 514 0.432 515 0.090
516 0.518 517 0.236 518 0.480 519 0.400 520 0.174 525 0.200 526
0.802 528 0.203 529 0.107 550 0.157 551 0.135 552 0.157 553 0.174
555 0.118 556 0.001 557 0.280 558 0.087 559 0.141 560 0.071 561
0.060 562 0.375 563 0.559 564 0.610 565 0.720 566 0.550 567 0.200
568 0.658 569 0.237 572 0.238 574 0.045 575 0.337 576 0.086 577
0.087 585 0.280 584 0.130 590 0.490 591 0.880 594 0.880 596 0.510
597 0.230 598 0.290 601 0.230 602 0.290 620 0.70 622 0.290 623
0.400 624 0.410 633 0.750 648 0.130 649 0.160 650 0.220 651 0.120
652 0.200 654 0.270 655 0.080 656 0.150 657 0.080
INDUSTRIAL APPLICABILITY
[1860] The novel [1,2,4]triazolo[4,3-a]quinoxaline derivative
provided in an aspect of the present invention, inhibits the
binding of BRD4, one of BET protein family, at a low concentration,
and displays excellent cytotoxicity in tumor cells, so that it can
be used as a pharmaceutical composition for the prevention or
treatment of BET protein related diseases including cancer and
autoimmune disease.
* * * * *